Is ACTG1 p.Lys50Arg (c.149A>G) pathogenic?

ACTG1 p.Lys50Arg (c.149A>G) is classified Uncertain significance in ACTG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-28). AlphaMissense: ambiguous (0.4366); Very rare (popmax 0.00167%, amr).

How common is ACTG1 p.Lys50Arg (c.149A>G) in the general population?

ACTG1 p.Lys50Arg (c.149A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ACTG1 p.Lys50Arg (c.149A>G)?

AlphaMissense predicts ambiguous (score 0.4366) — an in-silico prediction, not a clinical call.

ACTG1 p.Lys50Arg

c.149A>G · VCV3361436

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4366 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4366	ambiguous
REVEL	0.709	pathogenic-leaning
SaProt	LLR -12.95	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 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 367 bp · p 2.2e-06 · regional, not allelic
Overall
CADD	25.5	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 0.00167% Admixed American · 1/60,020 alleles

Overall 0.000124% 2/1,613,764 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,020
European (non-Finnish)	8.47e-05%	1,180,013

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: ACTG1
Protein: p.Lys50Arg
Coding: c.149A>G
MANE Select: NM_001614
Type: single nucleotide variant
Location: chr17:81512117 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 95.44 · 11 PDB
Residue 50: a cross-link site

Full ACTG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTG1 p.Lys50= Likely benign ★★ same residue
ACTG1 p.Ala135Val Pathogenic/Likely pathogenic ★★ same type
ACTG1 p.Ala204Gly Likely pathogenic ★★ same type
ACTG1 p.Arg183Gln Pathogenic/Likely pathogenic ★★ same type
ACTG1 p.Arg183Trp Pathogenic/Likely pathogenic ★★ same type
ACTG1 p.Arg206Gln Pathogenic/Likely pathogenic ★★ same type
ACTG1 p.Arg210Cys Pathogenic ★★ same type
ACTG1 p.Arg254Trp Pathogenic/Likely pathogenic ★★ 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/actg1-p-lys50arg (accessed [today's date]).

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