Is TRIM25 p.Arg231Trp (c.691C>T) pathogenic?

TRIM25 p.Arg231Trp (c.691C>T) is classified Uncertain significance in TRIM25 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely benign (0.1311); Very rare (popmax 0.00439%, sas).

How common is TRIM25 p.Arg231Trp (c.691C>T) in the general population?

TRIM25 p.Arg231Trp (c.691C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about TRIM25 p.Arg231Trp (c.691C>T)?

AlphaMissense predicts likely benign (score 0.1311) — an in-silico prediction, not a clinical call.

TRIM25 p.Arg231Trp

c.691C>T · rs764695048 · VCV3182314

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1311 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1311	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -9.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.6	GERP 0.82, phastCons 0.98
Regional constraint	o/e 0.83	unconstrained · MANE · 17 kb · p 0.00013 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,082 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000806% 13/1,613,502 alleles · very rare exomes 10/1,461,360 · genomes 3/152,142 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,770
Admixed American	0.00333%	30,002
East Asian	0.00223%	44,894
African / African-American	0.00134%	74,890
European (non-Finnish)	0.000424%	235,997

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: TRIM25
Protein: p.Arg231Trp
Coding: c.691C>T
MANE Select: NM_005082
dbSNP: rs764695048
Type: single nucleotide variant
Location: chr17:56908470 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.78 · 10 PDB
Residue 231: the 'interaction with influenza a virus ns1' region; an α-helix

Full TRIM25 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRIM25 p.Ala216= Benign ★★ same type
TRIM25 p.Thr185Ala Benign ★★ same type
TRIM25 p.Thr575= Benign ★★ same type
TRIM25 p.Ala114Val Uncertain significance ★ ⚠ same type
TRIM25 p.Ala124Val Uncertain significance ★ same type
TRIM25 p.Ala254Thr Uncertain significance ★ ⚠ same type
TRIM25 p.Ala424Ser Uncertain significance ★ ⚠ same type
TRIM25 p.Ala424Val 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/trim25-p-arg231trp (accessed [today's date]).

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