Is ACTRT1 p.Arg313Thr (c.938G>C) pathogenic?

ACTRT1 p.Arg313Thr (c.938G>C) is classified Uncertain significance in ACTRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-14). AlphaMissense: likely pathogenic (0.8003); Very rare (popmax 0.00353%, afr).

How common is ACTRT1 p.Arg313Thr (c.938G>C) in the general population?

ACTRT1 p.Arg313Thr (c.938G>C) is very rare (popmax 0.00353%, afr) (gnomAD).

What do computational predictors say about ACTRT1 p.Arg313Thr (c.938G>C)?

AlphaMissense predicts likely pathogenic (score 0.8003) — an in-silico prediction, not a clinical call.

ACTRT1 p.Arg313Thr

c.938G>C · rs376216938 · VCV2470480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8003 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00353%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8003	likely pathogenic · top 6% in ACTRT1
REVEL	0.787	moderately pathogenic-leaning
SaProt	LLR -13.98	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	phastCons 0.32
Regional constraint	o/e 1.15	unconstrained · MANE · 1,127 bp · p 0.013 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00353% African / African-American · 2/56,600 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.00248% 30/1,208,214 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00353%	28,300
European (non-Finnish)	0.00302%	33,145
Remaining individualsnot grpmax-eligible	0.0021%	47,553

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.Arg313Thr
Coding: c.938G>C
MANE Select: NM_138289
dbSNP: rs376216938
Type: single nucleotide variant
Location: chrX:128051269 (GRCh38)
Structure: AlphaFold pLDDT 92.94
Residue 313: a UniProt-annotated variant site (found in a patient with bazex syndrome; uncertain significance)

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

Similar variants

ACTRT1 p.Arg313Ser Benign ★★ same residue
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-arg313thr (accessed [today's date]).

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