Is ACTA1 p.Glu6Ter (c.16G>T) pathogenic?

ACTA1 p.Glu6Ter (c.16G>T) is classified Likely pathogenic in ACTA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-03). Very rare (popmax 0.00133%, afr).

How common is ACTA1 p.Glu6Ter (c.16G>T) in the general population?

ACTA1 p.Glu6Ter (c.16G>T) is very rare (popmax 0.00133%, afr) (gnomAD).

ACTA1 p.Glu6Ter

c.16G>T · VCV4081088

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 7
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Overall
CADD	47.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,068 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,461,814 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,068
European (non-Finnish)	0.000339%	295,002

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: ACTA1
Protein: p.Glu6Ter
Coding: c.16G>T
MANE Select: NM_001100
Type: single nucleotide variant
Location: chr1:229433100 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.21 · 5 PDB

Full ACTA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTA1 p.Glu6Lys Pathogenic/Likely pathogenic ★★ same residue
ACTA1 c.617-5C>A Likely pathogenic ★★★ same type
ACTA1 c.990+1G>T Pathogenic ★★★ same type
ACTA1 p.Asp13Asn Likely pathogenic ★★★ same type
ACTA1 p.Asp290His Pathogenic ★★★ same type
ACTA1 p.Asp58Asn Likely pathogenic ★★★ same type
ACTA1 p.Cys376Phe Likely pathogenic ★★★ same type
ACTA1 p.Cys376Ser 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/acta1-p-glu6ter (accessed [today's date]).

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