Is ACTRT1 p.Thr129Ala (c.385A>G) pathogenic?

ACTRT1 p.Thr129Ala (c.385A>G) is classified Uncertain significance in ACTRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.0845); Very rare (popmax 0.000112%, nfe).

How common is ACTRT1 p.Thr129Ala (c.385A>G) in the general population?

ACTRT1 p.Thr129Ala (c.385A>G) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about ACTRT1 p.Thr129Ala (c.385A>G)?

AlphaMissense predicts likely benign (score 0.0845) — an in-silico prediction, not a clinical call.

ACTRT1 p.Thr129Ala

c.385A>G · VCV4637204

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0845	likely benign
REVEL	0.404	indeterminate
SaProt	LLR -8.82	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 1,127 bp · p 0.013 · regional, not allelic
Overall
CADD	15.82	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/895,374 alleles

Overall 9.11e-05% 1/1,098,088 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: ACTRT1
Protein: p.Thr129Ala
Coding: c.385A>G
MANE Select: NM_138289
Type: single nucleotide variant
Location: chrX:128051822 (GRCh38)
Structure: AlphaFold pLDDT 92.94

Full ACTRT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTRT1 p.Arg313Ser Benign ★★ same type
ACTRT1 p.Ser345Thr Benign ★★ ⚠ same type
ACTRT1 p.Ala141Val Uncertain significance ★ ⚠ same type
ACTRT1 p.Ala344Val Uncertain significance ★ ⚠ same type
ACTRT1 p.Ala361Glu Uncertain significance ★ ⚠ same type
ACTRT1 p.Arg194Leu Uncertain significance ★ ⚠ same type
ACTRT1 p.Arg194Trp Uncertain significance ★ ⚠ same type
ACTRT1 p.Arg231Leu 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/actrt1-p-thr129ala (accessed [today's date]).

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