Is STRAP p.Leu238Val (c.712C>G) pathogenic?

STRAP p.Leu238Val (c.712C>G) is classified Uncertain significance in STRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: likely benign (0.0798); Very rare (popmax 0.00345%, amr).

How common is STRAP p.Leu238Val (c.712C>G) in the general population?

STRAP p.Leu238Val (c.712C>G) is very rare (popmax 0.00345%, amr) (gnomAD).

What do computational predictors say about STRAP p.Leu238Val (c.712C>G)?

AlphaMissense predicts likely benign (score 0.0798) — an in-silico prediction, not a clinical call.

STRAP p.Leu238Val

c.712C>G · VCV4177077

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0798 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00345%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0798	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -6.43	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 1.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 8,013 bp · p 0.022 · regional, not allelic
Overall
CADD	19.45	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 0.00345% Admixed American · 2/57,912 alleles

Filtering AF 0.000573% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000214%

Overall 0.000187% 3/1,602,896 alleles · very rare exomes 3/1,450,838 · genomes 0/152,058 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00345%	28,956
Remaining individualsnot grpmax-eligible	0.00161%	62,020

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.Leu238Val
Coding: c.712C>G
MANE Select: NM_007178
Type: single nucleotide variant
Location: chr12:15897955 (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-leu238val (accessed [today's date]).

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