Is TRNT1 p.Phe167Ser (c.500T>C) pathogenic?

TRNT1 p.Phe167Ser (c.500T>C) is classified Uncertain significance in TRNT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-14). AlphaMissense: ambiguous (0.416); Ultra-rare (popmax 0.0529%, afr); Associated with Inborn genetic diseases.

What condition is associated with TRNT1 p.Phe167Ser (c.500T>C)?

TRNT1 p.Phe167Ser (c.500T>C) is associated with Inborn genetic diseases, congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome (ClinVar).

How common is TRNT1 p.Phe167Ser (c.500T>C) in the general population?

TRNT1 p.Phe167Ser (c.500T>C) is ultra-rare (popmax 0.0529%, afr) (gnomAD).

What do computational predictors say about TRNT1 p.Phe167Ser (c.500T>C)?

AlphaMissense predicts ambiguous (score 0.416) — an in-silico prediction, not a clinical call.

TRNT1 p.Phe167Ser

c.500T>C · rs145784140 · VCV1504700

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.416 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0529%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.416	ambiguous
REVEL	0.148	moderately benign-leaning
SaProt	LLR -9.86	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -1.6, phastCons 0.98
Regional constraint	o/e 1.25	unconstrained · MANE · 19 kb · p 1e-08 · regional, not allelic
Overall
CADD	23.4	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 0.0529% African / African-American · 39/73,710 alleles

Filtering AF 0.0398% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0351%

Overall 0.00309% 49/1,583,706 alleles · ultra-rare exomes 34/1,431,474 · genomes 15/152,232 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0529%	1,890
Admixed American	0.0071%	14,080
Remaining individualsnot grpmax-eligible	0.00655%	15,260
South Asian	0.00114%	87,508
European (non-Finnish)	8.61e-05%	1,161,968

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.Phe167Ser
Coding: c.500T>C
MANE Select: NM_182916
dbSNP: rs145784140
Type: single nucleotide variant
Location: chr3:3144602 (GRCh38)
Gene constraint: LOEUF 1.232 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.00 · 3 PDB
Residue 167: a β-strand

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

Disease context

Inborn genetic diseases — 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.Phe167Leu Uncertain significance ★ ⚠ same residue
TRNT1 p.Phe167fs Pathogenic/Likely 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
TRNT1 p.Ala273Gly Uncertain significance ★★ ⚠ 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-phe167ser (accessed [today's date]).

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