Is ACTRT1 p.Arg313Ser (c.939G>T) pathogenic?

ACTRT1 p.Arg313Ser (c.939G>T) is classified Benign in ACTRT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-03-30). AlphaMissense: likely pathogenic (0.8968); Low-frequency (popmax 3.5%, afr).

How common is ACTRT1 p.Arg313Ser (c.939G>T) in the general population?

ACTRT1 p.Arg313Ser (c.939G>T) is low-frequency (popmax 3.5%, afr) (gnomAD).

What do computational predictors say about ACTRT1 p.Arg313Ser (c.939G>T)?

AlphaMissense predicts likely pathogenic (score 0.8968) — an in-silico prediction, not a clinical call.

ACTRT1 p.Arg313Ser

c.939G>T · rs61741364 · VCV720067

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8968 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.5%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8968	likely pathogenic · top 2% in ACTRT1
REVEL	0.54	indeterminate
SaProt	LLR -13.29	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4
Regional constraint	o/e 1.15	unconstrained · MANE · 1,127 bp · p 0.013 · regional, not allelic
Overall
CADD	8.211	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 3.5% African / African-American · 1,979/56,614 alleles

Filtering AF 3.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.32%

Overall 0.187% 2,259/1,208,169 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.5%	29
Admixed American	0.251%	399
Remaining individualsnot grpmax-eligible	0.25%	400
Middle Eastern	0.161%	622
South Asian	0.0106%	9,438
European (non-Finnish)	0.0038%	26,320

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.Arg313Ser
Coding: c.939G>T
MANE Select: NM_138289
dbSNP: rs61741364
Type: single nucleotide variant
Location: chrX:128051268 (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.Arg313Thr Uncertain significance ★ ⚠ 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-arg313ser (accessed [today's date]).

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