Is STAP1 p.Met2Thr (c.5T>C) pathogenic?

STAP1 p.Met2Thr (c.5T>C) is classified Benign in STAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-20). AlphaMissense: likely benign (0.2474); Low-frequency (popmax 1.19%, eas); Associated with STAP1-related disorder.

What condition is associated with STAP1 p.Met2Thr (c.5T>C)?

STAP1 p.Met2Thr (c.5T>C) is associated with STAP1-related disorder (ClinVar).

How common is STAP1 p.Met2Thr (c.5T>C) in the general population?

STAP1 p.Met2Thr (c.5T>C) is low-frequency (popmax 1.19%, eas) (gnomAD).

What do computational predictors say about STAP1 p.Met2Thr (c.5T>C)?

AlphaMissense predicts likely benign (score 0.2474) — an in-silico prediction, not a clinical call.

STAP1 p.Met2Thr

c.5T>C · rs141604937 · VCV3046099

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2474 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.19%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

STAP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.2474	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -5.47	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 6	GERP 1.9, phastCons 1
Overall
CADD	22.8	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 1.19% East Asian · 532/44,850 alleles

Filtering AF 1.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.07%

Overall 0.0381% 614/1,613,110 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.19%	84
Remaining individualsnot grpmax-eligible	0.107%	932
South Asian	0.011%	9,097
Admixed American	0.00835%	11,976

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.Met2Thr
Coding: c.5T>C
MANE Select: NM_004182 · reported on NM_012108
dbSNP: rs141604937
Type: single nucleotide variant
Location: chr4:67558814 (GRCh38)
Structure: AlphaFold pLDDT 88.06

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

Disease context

STAP1-related disorder

Similar variants

UXT p.Ala2Ser Uncertain significance ★ ⚠ same residue
STAP1 p.Gln192Arg Uncertain significance ★★ ⚠ same condition
STAP1 p.Leu288Val Uncertain significance ★★ ⚠ same condition
STAP1 c.-3G>T Likely benign same condition
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

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-met2thr (accessed [today's date]).

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