Is STAP1 p.Ile215Val (c.643A>G) pathogenic?

STAP1 p.Ile215Val (c.643A>G) is classified Uncertain significance in STAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-16). AlphaMissense: likely benign (0.1124); Very rare (popmax 0.00535%, afr).

How common is STAP1 p.Ile215Val (c.643A>G) in the general population?

STAP1 p.Ile215Val (c.643A>G) is very rare (popmax 0.00535%, afr) (gnomAD).

What do computational predictors say about STAP1 p.Ile215Val (c.643A>G)?

AlphaMissense predicts likely benign (score 0.1124) — an in-silico prediction, not a clinical call.

STAP1 p.Ile215Val

c.643A>G · rs1183202563 · VCV3226195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1124 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00535%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1124	likely benign
REVEL	0.277	benign-leaning
SaProt	LLR -6.97	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 3.5	GERP 1.5, phastCons 0.99
Overall
CADD	18.69	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 0.00535% African / African-American · 4/74,794 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,612,332 alleles · very rare exomes 0/1,460,126 · genomes 4/152,206 · 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: STAP1
Protein: p.Ile215Val
Coding: c.643A>G
MANE Select: NM_012108
dbSNP: rs1183202563
Type: single nucleotide variant
Location: chr4:67583686 (GRCh38)
Structure: AlphaFold pLDDT 88.06

Full STAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

STAP1 p.Gln192Arg Uncertain significance ★★ ⚠ same type
STAP1 p.Leu288Val Uncertain significance ★★ ⚠ same type
STAP1 c.120+6T>C Benign/Likely benign ★★ same type
STAP1 c.192+102T>C Likely benign ★★ same type
STAP1 c.192+10T>C Benign ★★ same type
STAP1 c.530+11A>G Benign ★★ same type
STAP1 c.530+60A>G Benign ★★ same type
STAP1 c.730-41G>C Benign ★★ 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/stap1-p-ile215val (accessed [today's date]).

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