Is STAP1 p.Glu239Lys (c.715G>A) pathogenic?

STAP1 p.Glu239Lys (c.715G>A) is classified Uncertain significance in STAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-05). AlphaMissense: ambiguous (0.3703); Very rare (popmax 8.48e-05%, nfe).

How common is STAP1 p.Glu239Lys (c.715G>A) in the general population?

STAP1 p.Glu239Lys (c.715G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about STAP1 p.Glu239Lys (c.715G>A)?

AlphaMissense predicts ambiguous (score 0.3703) — an in-silico prediction, not a clinical call.

STAP1 p.Glu239Lys

c.715G>A · VCV4590303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3703 · ACMG-weighted

gnomAD v4.1

Rare

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

Computational evidence

Protein change
AlphaMissense	0.3703	ambiguous
REVEL	0.531	indeterminate
SaProt	LLR -12.72	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Overall
CADD	25.5	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) · 1/1,178,636 alleles

Overall 6.21e-05% 1/1,611,094 alleles · very rare exomes 1/1,458,998 · genomes 0/152,096 · 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.Glu239Lys
Coding: c.715G>A
MANE Select: NM_012108
Type: single nucleotide variant
Location: chr4:67590939 (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-glu239lys (accessed [today's date]).

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