Is STAP1 p.Ile150Thr (c.449T>C) pathogenic?

STAP1 p.Ile150Thr (c.449T>C) is classified Uncertain significance in STAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-04). AlphaMissense: likely benign (0.0508); Ultra-rare (popmax 0.0242%, sas).

How common is STAP1 p.Ile150Thr (c.449T>C) in the general population?

STAP1 p.Ile150Thr (c.449T>C) is ultra-rare (popmax 0.0242%, sas) (gnomAD).

What do computational predictors say about STAP1 p.Ile150Thr (c.449T>C)?

AlphaMissense predicts likely benign (score 0.0508) — an in-silico prediction, not a clinical call.

STAP1 p.Ile150Thr

c.449T>C · rs779496091 · VCV3226192

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0508 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0508	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -6.18	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 -0.091	GERP -5.3
Overall
CADD	12.97	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 0.0242% South Asian · 22/91,058 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00192% 31/1,613,852 alleles · ultra-rare exomes 30/1,461,766 · genomes 1/152,086 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0242%	4,139
Remaining individualsnot grpmax-eligible	0.0032%	31,240
Finnishnot grpmax-eligible	0.00312%	32,011
European (non-Finnish)	0.000424%	235,990

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.Ile150Thr
Coding: c.449T>C
MANE Select: NM_012108
dbSNP: rs779496091
Type: single nucleotide variant
Location: chr4:67581390 (GRCh38)
Structure: AlphaFold pLDDT 88.06

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

Similar variants

STAP1 p.Ile150= Likely benign ★ same residue
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

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-ile150thr (accessed [today's date]).

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