Is ACTL6A p.Val187= (c.561C>T) pathogenic?

ACTL6A p.Val187= (c.561C>T) is classified Likely benign in ACTL6A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-01). Very rare (popmax 0.00224%, eas).

How common is ACTL6A p.Val187= (c.561C>T) in the general population?

ACTL6A p.Val187= (c.561C>T) is very rare (popmax 0.00224%, eas) (gnomAD).

ACTL6A p.Val187=

c.561C>T · rs368778776 · VCV2654290

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -0.69, phastCons 1
Overall
CADD	8.842	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,674 alleles

Filtering AF 0.000691% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000541%

Overall 0.001% 16/1,596,708 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,674
Remaining individualsnot grpmax-eligible	0.00162%	61,726
European (non-Finnish)	0.00119%	83,921

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.Val187=
Coding: c.561C>T
MANE Select: NM_004301
dbSNP: rs368778776
Type: single nucleotide variant
Location: chr3:179576301 (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

Similar variants

ACTL6A p.Arg389Trp Uncertain significance ★★ ⚠ same type
ACTL6A p.Arg390Ser Uncertain significance ★★ ⚠ same type
ACTL6A p.Asp339= Benign ★★ same type
ACTL6A c.1209+1G>C Uncertain significance ★ same type
ACTL6A c.477-1G>C Uncertain significance ★ same type
ACTL6A c.477-2A>G Uncertain significance ★ same type
ACTL6A c.572-4A>G Uncertain significance ★ same type
ACTL6A c.768+1G>A 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/actl6a-p-val187 (accessed [today's date]).

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