Is ACTR8 p.Arg77Gln (c.230G>A) pathogenic?

ACTR8 p.Arg77Gln (c.230G>A) is classified Uncertain significance in ACTR8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-14). AlphaMissense: ambiguous (0.4783); Ultra-rare (popmax 0.0657%, mid).

How common is ACTR8 p.Arg77Gln (c.230G>A) in the general population?

ACTR8 p.Arg77Gln (c.230G>A) is ultra-rare (popmax 0.0657%, mid) (gnomAD).

What do computational predictors say about ACTR8 p.Arg77Gln (c.230G>A)?

AlphaMissense predicts ambiguous (score 0.4783) — an in-silico prediction, not a clinical call.

ACTR8 p.Arg77Gln

c.230G>A · rs752053283 · VCV2351068

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4783 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4783	ambiguous
REVEL	0.809	moderately pathogenic-leaning
SaProt	LLR -14.27	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 6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 13 kb · p 0.0002 · regional, not allelic
Overall
CADD	32.0	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 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00229% 37/1,613,948 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
African / African-American	0.00267%	37,454
European (non-Finnish)	0.00254%	39,333
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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: ACTR8
Protein: p.Arg77Gln
Coding: c.230G>A
MANE Select: NM_022899
dbSNP: rs752053283
Type: single nucleotide variant
Location: chr3:53880003 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.30 · 1 PDB
Residue 77: a β-strand

Full ACTR8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTR8 c.406-7T>G Benign ★★ same type
ACTR8 p.Ala171Ser Uncertain significance ★ ⚠ same type
ACTR8 p.Ala270Thr Uncertain significance ★ ⚠ same type
ACTR8 p.Ala388Ser Uncertain significance ★ ⚠ same type
ACTR8 p.Ala427Ser Uncertain significance ★ ⚠ same type
ACTR8 p.Ala436Glu Uncertain significance ★ ⚠ same type
ACTR8 p.Ala483Val Uncertain significance ★ ⚠ same type
ACTR8 p.Ala585Pro 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/actr8-p-arg77gln (accessed [today's date]).

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