Is ACTL7B p.Ala308Val (c.923C>T) pathogenic?

ACTL7B p.Ala308Val (c.923C>T) is classified Likely benign in ACTL7B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely benign (0.0663); Very rare (popmax 0.00866%, amr).

How common is ACTL7B p.Ala308Val (c.923C>T) in the general population?

ACTL7B p.Ala308Val (c.923C>T) is very rare (popmax 0.00866%, amr) (gnomAD).

What do computational predictors say about ACTL7B p.Ala308Val (c.923C>T)?

AlphaMissense predicts likely benign (score 0.0663) — an in-silico prediction, not a clinical call.

ACTL7B p.Ala308Val

c.923C>T · rs1271933655 · VCV2207735

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0663 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00866%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0663	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -4.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.38	donor gain · deltas
Constraint at this position
Conservation	phyloP 0.59	GERP -2.6
Regional constraint	o/e 1.04	unconstrained · MANE · 1,244 bp · p 0.29 · regional, not allelic
Overall
CADD	0.545	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 0.00866% Admixed American · 4/46,170 alleles

Filtering AF 0.00292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.000395% 6/1,517,764 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00866%	11,543
European (non-Finnish)	0.000177%	565,937

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: ACTL7B
Protein: p.Ala308Val
Coding: c.923C>T
MANE Select: NM_006686
dbSNP: rs1271933655
Type: single nucleotide variant
Location: chr9:108855008 (GRCh38)
Gene constraint: LOEUF 1.414 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.35

Full ACTL7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTL7B p.Ala263= Benign ★★ same type
ACTL7B p.Ala164Thr Uncertain significance ★ ⚠ same type
ACTL7B p.Ala240Val Uncertain significance ★ ⚠ same type
ACTL7B p.Ala243Thr Uncertain significance ★ ⚠ same type
ACTL7B p.Ala28Val Uncertain significance ★ ⚠ same type
ACTL7B p.Ala2Val Uncertain significance ★ ⚠ same type
ACTL7B p.Ala36Gly Uncertain significance ★ ⚠ same type
ACTL7B p.Ala388Ser 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/actl7b-p-ala308val (accessed [today's date]).

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