Is ACTRT3 p.Ser260Tyr (c.779C>A) pathogenic?

ACTRT3 p.Ser260Tyr (c.779C>A) is classified Uncertain significance in ACTRT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.0954); Absent from gnomAD v4.1.

How common is ACTRT3 p.Ser260Tyr (c.779C>A) in the general population?

ACTRT3 p.Ser260Tyr (c.779C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTRT3 p.Ser260Tyr (c.779C>A)?

AlphaMissense predicts likely benign (score 0.0954) — an in-silico prediction, not a clinical call.

ACTRT3 p.Ser260Tyr

c.779C>A · rs763887085 · VCV3142920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0954 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0954	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -7.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -3.6, phastCons 0.28
Regional constraint	o/e 0.98	unconstrained · MANE · 2,085 bp · p 0.65 · regional, not allelic
Overall
CADD	11.11	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

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: ACTRT3
Protein: p.Ser260Tyr
Coding: c.779C>A
MANE Select: NM_032487
dbSNP: rs763887085
Type: single nucleotide variant
Location: chr3:169767772 (GRCh38)
Gene constraint: LOEUF 1.242 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.47

Full ACTRT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTRT3 p.Ala108Val Uncertain significance ★ ⚠ same type
ACTRT3 p.Ala257Val Uncertain significance ★ ⚠ same type
ACTRT3 p.Ala315Val Uncertain significance ★ ⚠ same type
ACTRT3 p.Ala318Ser Uncertain significance ★ ⚠ same type
ACTRT3 p.Ala323Thr Uncertain significance ★ ⚠ same type
ACTRT3 p.Arg205Ser Uncertain significance ★ ⚠ same type
ACTRT3 p.Arg25Trp Uncertain significance ★ ⚠ same type
ACTRT3 p.Arg309Trp 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/actrt3-p-ser260tyr (accessed [today's date]).

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