Is TPRN p.Arg156= (c.468C>T) pathogenic?

TPRN p.Arg156= (c.468C>T) is classified Likely benign in TPRN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). Rare (popmax 0.105%, mid).

How common is TPRN p.Arg156= (c.468C>T) in the general population?

TPRN p.Arg156= (c.468C>T) is rare (popmax 0.105%, mid) (gnomAD).

TPRN p.Arg156=

c.468C>T · rs1426776081 · VCV1443078

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.105%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.029	GERP -1.6, phastCons 0.1
Overall
CADD	3.685	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% Middle Eastern · 2/1,908 alleles

Filtering AF 0.0342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0294%

Overall 0.0036% 35/972,686 alleles · rare exomes 15/829,272 · genomes 20/143,414 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.105%	954
African / African-American	0.0485%	2,063
Remaining individualsnot grpmax-eligible	0.0137%	7,289
Admixed American	0.00643%	15,552
European (non-Finnish)	0.000122%	822,477

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: TPRN
Protein: p.Arg156=
Coding: c.468C>T
MANE Select: NM_001128228
dbSNP: rs1426776081
Type: single nucleotide variant
Location: chr9:137200244 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.27 · 1 PDB
Residue 156: the 'disordered' region

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

Similar variants

TPRN p.Arg156His Uncertain significance ★ ⚠ same residue
TPRN p.Gln414Ter Pathogenic ★★ same type
TPRN c.1725+5G>A Uncertain significance ★★ same type
TPRN p.Ala191Val Uncertain significance ★★ ⚠ same type
TPRN p.Ala302Asp Uncertain significance ★★ ⚠ same type
TPRN p.Ala390Ser Uncertain significance ★★ ⚠ same type
TPRN p.Ala695Thr Uncertain significance ★★ ⚠ same type
TPRN p.Arg231Trp Uncertain significance ★★ ⚠ same type

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/tprn-p-arg156 (accessed [today's date]).

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