Is STRAP p.Met3Val (c.7A>G) pathogenic?

STRAP p.Met3Val (c.7A>G) is classified Uncertain significance in STRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). AlphaMissense: likely benign (0.2109); Ultra-rare (popmax 0.0267%, afr).

How common is STRAP p.Met3Val (c.7A>G) in the general population?

STRAP p.Met3Val (c.7A>G) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

What do computational predictors say about STRAP p.Met3Val (c.7A>G)?

AlphaMissense predicts likely benign (score 0.2109) — an in-silico prediction, not a clinical call.

STRAP p.Met3Val

c.7A>G · rs140693042 · VCV2222008

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2109 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2109	likely benign
REVEL	0.216	benign-leaning
SaProt	LLR -1.60	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 7.6	GERP 0.91, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 90 bp · p 0.19 · regional, not allelic
Overall
CADD	20.4	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 0.0267% African / African-American · 20/75,046 alleles

Filtering AF 0.0176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.0161% 260/1,610,812 alleles · ultra-rare exomes 236/1,458,508 · genomes 24/152,304 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,752
European (non-Finnish)	0.017%	5,897
Middle Eastern	0.0165%	6,058
Remaining individualsnot grpmax-eligible	0.016%	6,241
South Asian	0.0132%	7,556
Finnishnot grpmax-eligible	0.0113%	8,874
East Asian	0.0111%	8,970
Admixed American	0.00668%	14,960
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,562

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.Met3Val
Coding: c.7A>G
MANE Select: NM_007178
dbSNP: rs140693042
Type: single nucleotide variant
Location: chr12:15882714 (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-met3val (accessed [today's date]).

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