Is ASAP3 p.Ser761Pro (c.2281T>C) pathogenic?

ASAP3 p.Ser761Pro (c.2281T>C) is classified Uncertain significance in ASAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-21). AlphaMissense: likely benign (0.0746); Ultra-rare (popmax 0.0535%, eas).

How common is ASAP3 p.Ser761Pro (c.2281T>C) in the general population?

ASAP3 p.Ser761Pro (c.2281T>C) is ultra-rare (popmax 0.0535%, eas) (gnomAD).

What do computational predictors say about ASAP3 p.Ser761Pro (c.2281T>C)?

AlphaMissense predicts likely benign (score 0.0746) — an in-silico prediction, not a clinical call.

ASAP3 p.Ser761Pro

c.2281T>C · rs144367386 · VCV2390701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0746 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0535%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0746	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -6.37	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 3.2	GERP -0.19, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	19.19	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 0.0535% East Asian · 24/44,878 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.00229% 37/1,614,086 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0535%	1,870
Remaining individualsnot grpmax-eligible	0.008%	12,500
South Asian	0.00659%	15,179
African / African-American	0.00133%	75,038
European (non-Finnish)	8.47e-05%	1,179,993

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: ASAP3
Protein: p.Ser761Pro
Coding: c.2281T>C
MANE Select: NM_017707
dbSNP: rs144367386
Type: single nucleotide variant
Location: chr1:23433119 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.62 · 4 PDB
Residue 761: the 'disordered' region

Full ASAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASAP3 p.Ser761Phe Uncertain significance ★ ⚠ same residue
ASAP3 p.Asp314= Benign ★★ same type
ASAP3 p.Glu377Ala Benign ★★ ⚠ same type
ASAP3 p.Leu147= Benign ★★ same type
ASAP3 p.Ala103Thr Uncertain significance ★ ⚠ same type
ASAP3 p.Ala221Thr Uncertain significance ★ ⚠ same type
ASAP3 p.Ala244Val Uncertain significance ★ ⚠ same type
ASAP3 p.Ala415Val Uncertain significance ★ ⚠ 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/asap3-p-ser761pro (accessed [today's date]).

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