Is ASTE1 p.Ala239Val (c.716C>T) pathogenic?

ASTE1 p.Ala239Val (c.716C>T) is classified Likely benign in ASTE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-21). AlphaMissense: likely benign (0.0604); Very rare (popmax 0.00502%, amr).

How common is ASTE1 p.Ala239Val (c.716C>T) in the general population?

ASTE1 p.Ala239Val (c.716C>T) is very rare (popmax 0.00502%, amr) (gnomAD).

What do computational predictors say about ASTE1 p.Ala239Val (c.716C>T)?

AlphaMissense predicts likely benign (score 0.0604) — an in-silico prediction, not a clinical call.

ASTE1 p.Ala239Val

c.716C>T · rs1284748949 · VCV2239215

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0604 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00502%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0604	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -6.38	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 1.9	GERP -3.4, phastCons 0.58
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.0008 · regional, not allelic
Overall
CADD	7.965	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 0.00502% Admixed American · 3/59,790 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.00093% 15/1,612,406 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00502%	19,930
African / African-American	0.00268%	37,380
South Asian	0.0022%	45,468
Remaining individualsnot grpmax-eligible	0.0016%	62,392
European (non-Finnish)	0.000594%	168,464

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: ASTE1
Protein: p.Ala239Val
Coding: c.716C>T
MANE Select: NM_014065
dbSNP: rs1284748949
Type: single nucleotide variant
Location: chr3:131024591 (GRCh38)
Gene constraint: LOEUF 1.291 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.40

Full ASTE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASTE1 p.Ala239Thr Uncertain significance ★ ⚠ same residue
ASTE1 p.Ala202Thr Uncertain significance ★ ⚠ same type
ASTE1 p.Ala219Val Uncertain significance ★ ⚠ same type
ASTE1 p.Ala514Thr Uncertain significance ★ ⚠ same type
ASTE1 p.Ala69Pro Uncertain significance ★ ⚠ same type
ASTE1 p.Arg143Trp Uncertain significance ★ ⚠ same type
ASTE1 p.Arg240His Uncertain significance ★ ⚠ same type
ASTE1 p.Arg255Gln 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/aste1-p-ala239val (accessed [today's date]).

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