Is ACTL6A p.Asp57Val (c.170A>T) pathogenic?

ACTL6A p.Asp57Val (c.170A>T) is classified Uncertain significance in ACTL6A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: ambiguous (0.435); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with ACTL6A p.Asp57Val (c.170A>T)?

ACTL6A p.Asp57Val (c.170A>T) is associated with Inborn genetic diseases (ClinVar).

How common is ACTL6A p.Asp57Val (c.170A>T) in the general population?

ACTL6A p.Asp57Val (c.170A>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ACTL6A p.Asp57Val (c.170A>T)?

AlphaMissense predicts ambiguous (score 0.435) — an in-silico prediction, not a clinical call.

ACTL6A p.Asp57Val

c.170A>T · VCV3483710

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.435 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.435	ambiguous
REVEL	0.903	moderately pathogenic-leaning
SaProt	LLR -12.25	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 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 25 kb · p 5.7e-26 · regional, not allelic
Overall
CADD	29.0	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 0.00133% African / African-American · 1/75,040 alleles

Overall 6.84e-05% 1/1,461,856 alleles · very rare

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: ACTL6A
Protein: p.Asp57Val
Coding: c.170A>T
MANE Select: NM_004301
Type: single nucleotide variant
Location: chr3:179570134 (GRCh38)
Gene constraint: LOEUF 0.186 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.04 · 31 PDB

Full ACTL6A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACTL6A p.Arg390Ser Uncertain significance ★★ ⚠ same condition
ACTL6A c.572-4A>G Uncertain significance ★ same condition
ACTL6A p.Asn291Ser Uncertain significance ★ ⚠ same condition
ACTL6A p.Asp95Glu Uncertain significance ★ ⚠ same condition
ACTL6A p.Asp97Val Uncertain significance ★ ⚠ same condition
ACTL6A p.Gly29Ala Uncertain significance ★ ⚠ same condition
ACTL6A p.Gly307Arg Uncertain significance ★ ⚠ same condition
ACTL6A p.Gly324Arg Uncertain significance ★ ⚠ same condition

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/actl6a-p-asp57val (accessed [today's date]).

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