Is ACTRT1 p.Thr80Ala (c.238A>G) pathogenic?

ACTRT1 p.Thr80Ala (c.238A>G) is classified Uncertain significance in ACTRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely benign (0.0864); Ultra-rare (popmax 0.0304%, amr).

How common is ACTRT1 p.Thr80Ala (c.238A>G) in the general population?

ACTRT1 p.Thr80Ala (c.238A>G) is ultra-rare (popmax 0.0304%, amr) (gnomAD).

What do computational predictors say about ACTRT1 p.Thr80Ala (c.238A>G)?

AlphaMissense predicts likely benign (score 0.0864) — an in-silico prediction, not a clinical call.

ACTRT1 p.Thr80Ala

c.238A>G · VCV4637195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0864 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0304%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0864	likely benign
REVEL	0.429	indeterminate
SaProt	LLR -6.72	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 0.71	phastCons 0.012
Regional constraint	o/e 1.15	unconstrained · MANE · 1,127 bp · p 0.013 · regional, not allelic
Overall
CADD	15.33	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 0.0304% Admixed American · 14/46,066 alleles

Filtering AF 0.0184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00127% 14/1,098,102 alleles · ultra-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.Thr80Ala
Coding: c.238A>G
MANE Select: NM_138289
Type: single nucleotide variant
Location: chrX:128051969 (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-thr80ala (accessed [today's date]).

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