Is TRIM37 p.Ser809Pro (c.2425T>C) pathogenic?

TRIM37 p.Ser809Pro (c.2425T>C) is classified Uncertain significance in TRIM37 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.0853); Ultra-rare (popmax 0.0213%, afr); Associated with Inborn genetic diseases.

What condition is associated with TRIM37 p.Ser809Pro (c.2425T>C)?

TRIM37 p.Ser809Pro (c.2425T>C) is associated with Inborn genetic diseases (ClinVar).

How common is TRIM37 p.Ser809Pro (c.2425T>C) in the general population?

TRIM37 p.Ser809Pro (c.2425T>C) is ultra-rare (popmax 0.0213%, afr) (gnomAD).

What do computational predictors say about TRIM37 p.Ser809Pro (c.2425T>C)?

AlphaMissense predicts likely benign (score 0.0853) — an in-silico prediction, not a clinical call.

TRIM37 p.Ser809Pro

c.2425T>C · VCV4829667

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0853 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0853	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -8.15	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 4.4	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 29 kb · p 0.44 · regional, not allelic
Overall
CADD	19.23	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 0.0213% African / African-American · 16/74,964 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.000992% 16/1,613,698 alleles · ultra-rare exomes 8/1,461,610 · genomes 8/152,088 · joint denominator

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: TRIM37
Protein: p.Ser809Pro
Coding: c.2425T>C
MANE Select: NM_015294
Type: single nucleotide variant
Location: chr17:59015761 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.93 · 1 PDB
Residue 809: the 'disordered' region

Full TRIM37 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

Similar variants

TRIM37 p.Ala385Ser Uncertain significance ★★ ⚠ same condition
TRIM37 p.Ala683Thr Uncertain significance ★★ ⚠ same condition
TRIM37 p.Arg178His Uncertain significance ★★ ⚠ same condition
TRIM37 p.Arg180Gln Uncertain significance ★★ ⚠ same condition
TRIM37 p.Arg192Leu Uncertain significance ★★ ⚠ same condition
TRIM37 p.Arg230Gln Uncertain significance ★★ ⚠ same condition
TRIM37 p.Arg628Gln Uncertain significance ★★ ⚠ same condition
TRIM37 p.Arg775Gln 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/trim37-p-ser809pro (accessed [today's date]).

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