Is STRAP p.Val85Met (c.253G>A) pathogenic?

STRAP p.Val85Met (c.253G>A) is classified Uncertain significance in STRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: ambiguous (0.5575); Very rare (popmax 8.48e-05%, nfe).

How common is STRAP p.Val85Met (c.253G>A) in the general population?

STRAP p.Val85Met (c.253G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about STRAP p.Val85Met (c.253G>A)?

AlphaMissense predicts ambiguous (score 0.5575) — an in-silico prediction, not a clinical call.

STRAP p.Val85Met

c.253G>A · rs1288123069 · VCV3171585

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5575 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5575	ambiguous
REVEL	0.522	indeterminate
SaProt	LLR -11.91	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 7,155 bp · p 4.3e-07 · regional, not allelic
Overall
CADD	29.0	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 8.48e-05% European (non-Finnish) · 1/1,179,368 alleles

Overall 6.2e-05% 1/1,612,936 alleles · very rare exomes 0/1,460,908 · genomes 1/152,028 · 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: STRAP
Protein: p.Val85Met
Coding: c.253G>A
MANE Select: NM_007178
dbSNP: rs1288123069
Type: single nucleotide variant
Location: chr12:15889932 (GRCh38)
Gene constraint: LOEUF 0.567 · pLI 0.84 (gnomAD)
Structure: AlphaFold pLDDT 89.75

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

Similar variants

STRAP p.Ala149Val Uncertain significance ★ ⚠ same type
STRAP p.Ala211Val Uncertain significance ★ ⚠ same type
STRAP p.Ala35Gly Uncertain significance ★ ⚠ same type
STRAP p.Arg125Cys Uncertain significance ★ ⚠ same type
STRAP p.Asp163Glu Uncertain significance ★ ⚠ same type
STRAP p.Glu331Asp Uncertain significance ★ ⚠ same type
STRAP p.Gly24Arg Uncertain significance ★ ⚠ same type
STRAP p.Ile126Val 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/strap-p-val85met (accessed [today's date]).

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