Is ACCSL p.Gly429Val (c.1286G>T) pathogenic?

ACCSL p.Gly429Val (c.1286G>T) is classified Uncertain significance in ACCSL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-09). AlphaMissense: ambiguous (0.4388); Very rare (popmax 0.00127%, nfe).

How common is ACCSL p.Gly429Val (c.1286G>T) in the general population?

ACCSL p.Gly429Val (c.1286G>T) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about ACCSL p.Gly429Val (c.1286G>T)?

AlphaMissense predicts ambiguous (score 0.4388) — an in-silico prediction, not a clinical call.

ACCSL p.Gly429Val

c.1286G>T · rs371005272 · VCV2545387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4388 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4388	ambiguous
REVEL	0.766	pathogenic-leaning
SaProt	LLR -12.69	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 0.84, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 12 kb · p 0.012 · regional, not allelic
Overall
CADD	23.8	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 0.00127% European (non-Finnish) · 15/1,180,034 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000929% 15/1,614,010 alleles · very rare

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: ACCSL
Protein: p.Gly429Val
Coding: c.1286G>T
MANE Select: NM_001031854
dbSNP: rs371005272
Type: single nucleotide variant
Location: chr11:44056285 (GRCh38)
Gene constraint: LOEUF 1.037 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.52

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

Similar variants

ACCSL p.Ala111Val Uncertain significance ★ ⚠ same type
ACCSL p.Ala248Val Uncertain significance ★ ⚠ same type
ACCSL p.Ala460Val Uncertain significance ★ ⚠ same type
ACCSL p.Ala87Val Uncertain significance ★ ⚠ same type
ACCSL p.Arg102Ser Uncertain significance ★ ⚠ same type
ACCSL p.Arg133His Uncertain significance ★ ⚠ same type
ACCSL p.Arg138Cys Uncertain significance ★ ⚠ same type
ACCSL p.Arg214Gln 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/accsl-p-gly429val (accessed [today's date]).

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