Is STRAP p.Glu331Asp (c.993A>C) pathogenic?

STRAP p.Glu331Asp (c.993A>C) is classified Uncertain significance in STRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: likely benign (0.0919); Rare (popmax 0.207%, amr).

How common is STRAP p.Glu331Asp (c.993A>C) in the general population?

STRAP p.Glu331Asp (c.993A>C) is rare (popmax 0.207%, amr) (gnomAD).

What do computational predictors say about STRAP p.Glu331Asp (c.993A>C)?

AlphaMissense predicts likely benign (score 0.0919) — an in-silico prediction, not a clinical call.

STRAP p.Glu331Asp

c.993A>C · rs143931116 · VCV2324718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0919 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.207%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0919	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -7.25	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 3.6	GERP 0.45, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 2,024 bp · p 0.3 · regional, not allelic
Overall
CADD	19.13	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 0.207% Admixed American · 92/44,410 alleles

Filtering AF 0.173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.16%

Overall 0.0458% 686/1,496,890 alleles · rare exomes 616/1,351,268 · genomes 70/145,622 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.207%	483
Remaining individualsnot grpmax-eligible	0.0611%	1,637
European (non-Finnish)	0.0484%	2,066
Middle Eastern	0.0202%	4,942
African / African-American	0.0118%	8,485
Finnishnot grpmax-eligible	0.00221%	45,308

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.Glu331Asp
Coding: c.993A>C
MANE Select: NM_007178
dbSNP: rs143931116
Type: single nucleotide variant
Location: chr12:15902918 (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.Gly24Arg Uncertain significance ★ ⚠ same type
STRAP p.Ile126Val Uncertain significance ★ ⚠ same type
STRAP p.Ile192Val 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-glu331asp (accessed [today's date]).

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