Is STAP1 p.Ser196Cys (c.587C>G) pathogenic?

STAP1 p.Ser196Cys (c.587C>G) is classified Uncertain significance in STAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-25). AlphaMissense: likely benign (0.1011); Ultra-rare (popmax 0.0721%, afr).

How common is STAP1 p.Ser196Cys (c.587C>G) in the general population?

STAP1 p.Ser196Cys (c.587C>G) is ultra-rare (popmax 0.0721%, afr) (gnomAD).

What do computational predictors say about STAP1 p.Ser196Cys (c.587C>G)?

AlphaMissense predicts likely benign (score 0.1011) — an in-silico prediction, not a clinical call.

STAP1 p.Ser196Cys

c.587C>G · rs201684919 · VCV2211739

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1011 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0721%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1011	likely benign
REVEL	0.403	indeterminate
SaProt	LLR -7.57	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 2.6, phastCons 1
Overall
CADD	24.2	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 0.0721% African / African-American · 54/74,886 alleles

Filtering AF 0.0567% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0512%

Overall 0.0039% 63/1,613,732 alleles · ultra-rare exomes 42/1,461,632 · genomes 21/152,100 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0721%	1,387
Admixed American	0.00834%	11,996
Remaining individualsnot grpmax-eligible	0.0048%	20,825
European (non-Finnish)	8.48e-05%	1,179,870

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.Ser196Cys
Coding: c.587C>G
MANE Select: NM_012108
dbSNP: rs201684919
Type: single nucleotide variant
Location: chr4:67583630 (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-ser196cys (accessed [today's date]).

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