Is ACTBL2 p.Gly343Ala (c.1028G>C) pathogenic?

ACTBL2 p.Gly343Ala (c.1028G>C) is classified Uncertain significance in ACTBL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely pathogenic (0.9744); Absent from gnomAD v4.1.

How common is ACTBL2 p.Gly343Ala (c.1028G>C) in the general population?

ACTBL2 p.Gly343Ala (c.1028G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTBL2 p.Gly343Ala (c.1028G>C)?

AlphaMissense predicts likely pathogenic (score 0.9744) — an in-silico prediction, not a clinical call.

ACTBL2 p.Gly343Ala

c.1028G>C · rs993505995 · VCV3141197

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9744 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9744	likely pathogenic · top 9% in ACTBL2
REVEL	0.658	pathogenic-leaning
SaProt	LLR -11.35	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 1,127 bp · p 0.086 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: ACTBL2
Protein: p.Gly343Ala
Coding: c.1028G>C
MANE Select: NM_001017992
dbSNP: rs993505995
Type: single nucleotide variant
Location: chr5:57481680 (GRCh38)
Gene constraint: LOEUF 1.624 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.97

Full ACTBL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTBL2 p.Gly343Glu Uncertain significance ★ ⚠ same residue
ACTBL2 p.Ala171Pro Uncertain significance ★ ⚠ same type
ACTBL2 p.Ala171Ser Uncertain significance ★ ⚠ same type
ACTBL2 p.Ala171Val Uncertain significance ★ same type
ACTBL2 p.Ala27Asp Uncertain significance ★ ⚠ same type
ACTBL2 p.Ala296Val Uncertain significance ★ ⚠ same type
ACTBL2 p.Ala30Ser Uncertain significance ★ ⚠ same type
ACTBL2 p.Ala322Thr 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/actbl2-p-gly343ala (accessed [today's date]).

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