Is ASAP1 p.Val609Ile (c.1825G>A) pathogenic?

ASAP1 p.Val609Ile (c.1825G>A) is classified Uncertain significance in ASAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-22). AlphaMissense: likely benign (0.0945); Rare (popmax 0.199%, afr).

How common is ASAP1 p.Val609Ile (c.1825G>A) in the general population?

ASAP1 p.Val609Ile (c.1825G>A) is rare (popmax 0.199%, afr) (gnomAD).

What do computational predictors say about ASAP1 p.Val609Ile (c.1825G>A)?

AlphaMissense predicts likely benign (score 0.0945) — an in-silico prediction, not a clinical call.

ASAP1 p.Val609Ile

c.1825G>A · rs141017948 · VCV2344556

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0945 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.199%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0945	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -9.38	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 1.8	GERP 2.3, phastCons 0.94
Regional constraint	o/e 0.94	unconstrained · MANE · 39 kb · p 0.25 · regional, not allelic
Overall
CADD	24.8	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 0.199% African / African-American · 149/74,932 alleles

Filtering AF 0.173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.163%

Overall 0.0151% 243/1,613,686 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.199%	503
Admixed American	0.0367%	2,727
Remaining individualsnot grpmax-eligible	0.0352%	2,841
Middle Eastern	0.033%	3,031
South Asian	0.0154%	6,503
European (non-Finnish)	0.00271%	36,869
East Asian	0.00223%	44,866
Finnishnot grpmax-eligible	0.00156%	64,000

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.Val609Ile
Coding: c.1825G>A
MANE Select: NM_018482
dbSNP: rs141017948
Type: single nucleotide variant
Location: chr8:130118216 (GRCh38)
Gene constraint: LOEUF 0.439 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.05 · 5 PDB

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.Arg447Gln Uncertain significance ★ ⚠ same type
ASAP1 p.Arg710Ter Uncertain significance ★ same type
ASAP1 p.Arg764Gln 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-val609ile (accessed [today's date]).

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