Is ACTRT1 p.Ser339Tyr (c.1016C>A) pathogenic?

ACTRT1 p.Ser339Tyr (c.1016C>A) is classified Uncertain significance in ACTRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-02). AlphaMissense: likely benign (0.244); Absent from gnomAD v4.1.

How common is ACTRT1 p.Ser339Tyr (c.1016C>A) in the general population?

ACTRT1 p.Ser339Tyr (c.1016C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTRT1 p.Ser339Tyr (c.1016C>A)?

AlphaMissense predicts likely benign (score 0.244) — an in-silico prediction, not a clinical call.

ACTRT1 p.Ser339Tyr

c.1016C>A · rs1247761507 · VCV2493756

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.244 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.244	likely benign
REVEL	0.746	pathogenic-leaning
SaProt	LLR -10.45	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 1,127 bp · p 0.013 · regional, not allelic
Overall
CADD	21.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACTRT1
Protein: p.Ser339Tyr
Coding: c.1016C>A
MANE Select: NM_138289
dbSNP: rs1247761507
Type: single nucleotide variant
Location: chrX:128051191 (GRCh38)
Structure: AlphaFold pLDDT 92.94
Residue 339: 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 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-ser339tyr (accessed [today's date]).

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