Is TRIM25 p.Ser372Pro (c.1114T>C) pathogenic?

TRIM25 p.Ser372Pro (c.1114T>C) is classified Uncertain significance in TRIM25 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-31). AlphaMissense: likely benign (0.0597); Ultra-rare (popmax 0.0167%, amr).

How common is TRIM25 p.Ser372Pro (c.1114T>C) in the general population?

TRIM25 p.Ser372Pro (c.1114T>C) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about TRIM25 p.Ser372Pro (c.1114T>C)?

AlphaMissense predicts likely benign (score 0.0597) — an in-silico prediction, not a clinical call.

TRIM25 p.Ser372Pro

c.1114T>C · VCV3328669

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0597 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0597	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -5.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -3.5
Regional constraint	o/e 0.83	unconstrained · MANE · 17 kb · p 0.00013 · regional, not allelic
Overall
CADD	0.047	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 0.0167% Admixed American · 10/59,996 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00477% 77/1,613,902 alleles · ultra-rare exomes 73/1,461,868 · genomes 4/152,034 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,000
European (non-Finnish)	0.00542%	18,437
Remaining individualsnot grpmax-eligible	0.0048%	20,827

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.Ser372Pro
Coding: c.1114T>C
MANE Select: NM_005082
Type: single nucleotide variant
Location: chr17:56899154 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.78 · 10 PDB
Residue 372: the 'interaction with influenza a virus ns1' region; the 'disordered' region

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-ser372pro (accessed [today's date]).

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