Is ACTRT3 p.Arg205Ser (c.615A>T) pathogenic?

ACTRT3 p.Arg205Ser (c.615A>T) is classified Uncertain significance in ACTRT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). AlphaMissense: ambiguous (0.5324); Very rare (popmax 0.00667%, amr).

How common is ACTRT3 p.Arg205Ser (c.615A>T) in the general population?

ACTRT3 p.Arg205Ser (c.615A>T) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about ACTRT3 p.Arg205Ser (c.615A>T)?

AlphaMissense predicts ambiguous (score 0.5324) — an in-silico prediction, not a clinical call.

ACTRT3 p.Arg205Ser

c.615A>T · rs1778012639 · VCV3142907

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5324 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Computational evidence

Protein change
AlphaMissense	0.5324	ambiguous
REVEL	0.61	indeterminate
SaProt	LLR -10.04	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -3, phastCons 0.92
Regional constraint	o/e 0.98	unconstrained · MANE · 2,085 bp · p 0.65 · regional, not allelic
Overall
CADD	19.59	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 0.00667% Admixed American · 4/60,006 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000248% 4/1,614,110 alleles · very 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: ACTRT3
Protein: p.Arg205Ser
Coding: c.615A>T
MANE Select: NM_032487
dbSNP: rs1778012639
Type: single nucleotide variant
Location: chr3:169767936 (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.Arg25Trp Uncertain significance ★ ⚠ same type
ACTRT3 p.Arg309Trp Uncertain significance ★ ⚠ same type
ACTRT3 p.Arg370Ile 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-arg205ser (accessed [today's date]).

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