Is ACTR6 p.Asp331Val (c.992A>T) pathogenic?

ACTR6 p.Asp331Val (c.992A>T) is classified Uncertain significance in ACTR6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-10). AlphaMissense: ambiguous (0.373); Absent from gnomAD v4.1.

How common is ACTR6 p.Asp331Val (c.992A>T) in the general population?

ACTR6 p.Asp331Val (c.992A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTR6 p.Asp331Val (c.992A>T)?

AlphaMissense predicts ambiguous (score 0.373) — an in-silico prediction, not a clinical call.

ACTR6 p.Asp331Val

c.992A>T · rs2499691497 · VCV3142625

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.373 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.373	ambiguous
REVEL	0.234	benign-leaning
SaProt	LLR -11.35	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.1	GERP 1.7, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 23 kb · p 3.5e-09 · regional, not allelic
Overall
CADD	25.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACTR6
Protein: p.Asp331Val
Coding: c.992A>T
MANE Select: NM_022496
dbSNP: rs2499691497
Type: single nucleotide variant
Location: chr12:100220077 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.37 · 21 PDB
Residue 331: an α-helix

Full ACTR6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTR6 p.Arg172Trp Uncertain significance ★ ⚠ same type
ACTR6 p.Arg332Gln Uncertain significance ★ ⚠ same type
ACTR6 p.Arg332Trp Uncertain significance ★ ⚠ same type
ACTR6 p.Asn354Lys Uncertain significance ★ ⚠ same type
ACTR6 p.Asp138Asn Uncertain significance ★ ⚠ same type
ACTR6 p.Cys339Arg Uncertain significance ★ ⚠ same type
ACTR6 p.Gln204His Uncertain significance ★ ⚠ same type
ACTR6 p.Glu254Gln 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/actr6-p-asp331val (accessed [today's date]).

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