Is ACTBL2 p.Ala171Val (c.512C>T) pathogenic?

ACTBL2 p.Ala171Val (c.512C>T) is classified Uncertain significance in ACTBL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: ambiguous (0.4117); Rare (popmax 0.445%, mid).

How common is ACTBL2 p.Ala171Val (c.512C>T) in the general population?

ACTBL2 p.Ala171Val (c.512C>T) is rare (popmax 0.445%, mid) (gnomAD).

What do computational predictors say about ACTBL2 p.Ala171Val (c.512C>T)?

AlphaMissense predicts ambiguous (score 0.4117) — an in-silico prediction, not a clinical call.

ACTBL2 p.Ala171Val

c.512C>T · rs763832753 · VCV2362080

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4117 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.445%, mid)

Computational evidence

Protein change
AlphaMissense	0.4117	ambiguous
REVEL	0.375	indeterminate
SaProt	LLR -13.87	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 1,127 bp · p 0.086 · regional, not allelic
Overall
CADD	27.7	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 0.445% Middle Eastern · 27/6,062 alleles

Filtering AF 0.314% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.27%

Overall 0.0211% 341/1,614,140 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.445%	225
Ashkenazi Jewishnot grpmax-eligible	0.426%	235
South Asian	0.0769%	1,301
Remaining individualsnot grpmax-eligible	0.0416%	2,404
Admixed American	0.00833%	12,005
European (non-Finnish)	0.00729%	13,721
African / African-American	0.00133%	75,032

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: ACTBL2
Protein: p.Ala171Val
Coding: c.512C>T
MANE Select: NM_001017992
dbSNP: rs763832753
Type: single nucleotide variant
Location: chr5:57482196 (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.Ala171Pro Uncertain significance ★ ⚠ same residue
ACTBL2 p.Ala171Ser Uncertain significance ★ ⚠ same residue
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
ACTBL2 p.Arg178Leu Uncertain significance ★ ⚠ same type
ACTBL2 p.Arg207Leu 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-ala171val (accessed [today's date]).

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