Is TRNT1 p.Pro270Arg (c.809C>G) pathogenic?

TRNT1 p.Pro270Arg (c.809C>G) is classified Conflicting classifications of pathogenicity in TRNT1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-17). AlphaMissense: likely pathogenic (0.8217); Ultra-rare (popmax 0.0393%, nfe); Associated with retinitis pigmentosa and erythrocytic microcytosis.

What condition is associated with TRNT1 p.Pro270Arg (c.809C>G)?

TRNT1 p.Pro270Arg (c.809C>G) is associated with retinitis pigmentosa and erythrocytic microcytosis, congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome (ClinVar).

How common is TRNT1 p.Pro270Arg (c.809C>G) in the general population?

TRNT1 p.Pro270Arg (c.809C>G) is ultra-rare (popmax 0.0393%, nfe) (gnomAD).

What do computational predictors say about TRNT1 p.Pro270Arg (c.809C>G)?

AlphaMissense predicts likely pathogenic (score 0.8217) — an in-silico prediction, not a clinical call.

TRNT1 p.Pro270Arg

c.809C>G · rs187921784 · VCV784897

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.8217 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0393%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

retinitis pigmentosa and erythrocytic microcytosis

Computational evidence

Protein change
AlphaMissense	0.8217	likely pathogenic
REVEL	0.468	indeterminate
SaProt	LLR -15.56	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.5, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 19 kb · p 1e-08 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0393% European (non-Finnish) · 464/1,179,518 alleles

Filtering AF 0.0364% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0351%

Overall 0.0609% 983/1,613,244 alleles · ultra-rare exomes 829/1,461,038 · genomes 154/152,206 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.755%	133
Remaining individualsnot grpmax-eligible	0.0432%	2,313
European (non-Finnish)grpmax	0.0393%	2,542
Middle Eastern	0.0168%	5,954
Admixed American	0.00834%	11,997
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,588
East Asian	0.00223%	44,830
African / African-American	0.00133%	74,976

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TRNT1
Protein: p.Pro270Arg
Coding: c.809C>G
MANE Select: NM_182916
dbSNP: rs187921784
Type: single nucleotide variant
Location: chr3:3147456 (GRCh38)
Gene constraint: LOEUF 1.232 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.00 · 3 PDB
Residue 270: a UniProt-annotated variant site (in sifd; uncertain significance)

Full TRNT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa and erythrocytic microcytosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome

Similar variants

TRNT1 p.Pro270Ser Uncertain significance ★★ same residue
TRNT1 p.Pro270_Ala271insLysLeu Benign/Likely benign ★★ same residue
TRNT1 p.Pro270fs Pathogenic ★ same residue
TRNT1 p.Arg190Ile Pathogenic ★★ same condition
TRNT1 p.Arg412Ter Pathogenic/Likely pathogenic ★★ same condition
TRNT1 p.Glu277Ter Pathogenic/Likely pathogenic ★★ same condition
TRNT1 p.Ile223Thr Pathogenic ★★ same condition
TRNT1 p.Lys416Glu Pathogenic/Likely pathogenic ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/trnt1-p-pro270arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown