Is STAP1 p.Leu246= (c.738C>T) pathogenic?

STAP1 p.Leu246= (c.738C>T) is classified Likely benign in STAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-14). Rare (popmax 0.188%, afr).

How common is STAP1 p.Leu246= (c.738C>T) in the general population?

STAP1 p.Leu246= (c.738C>T) is rare (popmax 0.188%, afr) (gnomAD).

STAP1 p.Leu246=

c.738C>T · rs144841016 · VCV1758642

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.188%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.7	GERP -4.3, phastCons 0.009
Overall
CADD	3.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.188% African / African-American · 141/74,982 alleles

Filtering AF 0.163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.153%

Overall 0.00986% 159/1,612,482 alleles · rare exomes 77/1,460,182 · genomes 82/152,300 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.188%	532
Admixed American	0.02%	4,989
Remaining individualsnot grpmax-eligible	0.00961%	10,406

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.Leu246=
Coding: c.738C>T
MANE Select: NM_012108
dbSNP: rs144841016
Type: single nucleotide variant
Location: chr4:67593268 (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-leu246 (accessed [today's date]).

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