Is ASAP1 p.Arg447Gln (c.1340G>A) pathogenic?

ASAP1 p.Arg447Gln (c.1340G>A) is classified Uncertain significance in ASAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely benign (0.0858); Very rare (popmax 0.00329%, sas).

How common is ASAP1 p.Arg447Gln (c.1340G>A) in the general population?

ASAP1 p.Arg447Gln (c.1340G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about ASAP1 p.Arg447Gln (c.1340G>A)?

AlphaMissense predicts likely benign (score 0.0858) — an in-silico prediction, not a clinical call.

ASAP1 p.Arg447Gln

c.1340G>A · VCV4643292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0858 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0858	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -5.29	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 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 18 kb · p 4e-06 · regional, not allelic
Overall
CADD	28.3	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 0.00329% South Asian · 3/91,076 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000434% 7/1,613,880 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,359
African / African-American	0.00134%	74,860
European (non-Finnish)	0.000254%	393,328

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: ASAP1
Protein: p.Arg447Gln
Coding: c.1340G>A
MANE Select: NM_018482
Type: single nucleotide variant
Location: chr8:130127968 (GRCh38)
Gene constraint: LOEUF 0.439 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.05 · 5 PDB
Residue 447: the arf-gap domain

Full ASAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASAP1 p.Gln263= Benign ★★ same type
ASAP1 p.Ala1035Gly Uncertain significance ★ ⚠ same type
ASAP1 p.Ala429Val Uncertain significance ★ ⚠ same type
ASAP1 p.Ala914Gly Uncertain significance ★ ⚠ same type
ASAP1 p.Arg212His Uncertain significance ★ ⚠ same type
ASAP1 p.Arg710Ter Uncertain significance ★ same type
ASAP1 p.Arg764Gln Uncertain significance ★ ⚠ same type
ASAP1 p.Asn134Tyr 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/asap1-p-arg447gln (accessed [today's date]).

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