Is ACTR8 p.Ala388Ser (c.1162G>T) pathogenic?

ACTR8 p.Ala388Ser (c.1162G>T) is classified Uncertain significance in ACTR8 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-01-19). AlphaMissense: likely benign (0.3314); Ultra-rare (popmax 0.0122%, nfe).

How common is ACTR8 p.Ala388Ser (c.1162G>T) in the general population?

ACTR8 p.Ala388Ser (c.1162G>T) is ultra-rare (popmax 0.0122%, nfe) (gnomAD).

What do computational predictors say about ACTR8 p.Ala388Ser (c.1162G>T)?

AlphaMissense predicts likely benign (score 0.3314) — an in-silico prediction, not a clinical call.

ACTR8 p.Ala388Ser

c.1162G>T · rs201796393 · VCV2405352

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3314 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3314	likely benign
REVEL	0.806	moderately pathogenic-leaning
SaProt	LLR -11.89	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 13 kb · p 0.0002 · regional, not allelic
Overall
CADD	33.0	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 0.0122% European (non-Finnish) · 143/1,172,970 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00987%

Overall 0.00905% 144/1,591,552 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0122%	8,203
Remaining individualsnot grpmax-eligible	0.00163%	61,456

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.Ala388Ser
Coding: c.1162G>T
MANE Select: NM_022899
dbSNP: rs201796393
Type: single nucleotide variant
Location: chr3:53872524 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.30 · 1 PDB
Residue 388: an α-helix

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.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
ACTR8 p.Ala593Pro 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-ala388ser (accessed [today's date]).

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