Is ACTRT2 p.Ala361= (c.1083C>T) pathogenic?

ACTRT2 p.Ala361= (c.1083C>T) is classified Likely benign in ACTRT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). Very rare (popmax 0.00446%, eas).

How common is ACTRT2 p.Ala361= (c.1083C>T) in the general population?

ACTRT2 p.Ala361= (c.1083C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

ACTRT2 p.Ala361=

c.1083C>T · VCV4223285

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -16	GERP -4.3
Overall
CADD	0.026	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,852 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00297% 48/1,613,762 alleles · very rare exomes 42/1,461,678 · genomes 6/152,084 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,426
European (non-Finnish)	0.00364%	27,442
Remaining individualsnot grpmax-eligible	0.0016%	62,476
African / African-American	0.00133%	74,914
South Asian	0.0011%	91,072

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: ACTRT2
Protein: p.Ala361=
Coding: c.1083C>T
MANE Select: NM_080431
Type: single nucleotide variant
Location: chr1:3022769 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 93.42

Full ACTRT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTRT2 p.Ala361Thr Uncertain significance ★ ⚠ same residue
ACTRT2 p.Ala135Val Uncertain significance ★ ⚠ same type
ACTRT2 p.Ala178Thr Uncertain significance ★ ⚠ same type
ACTRT2 p.Ala224Asp Uncertain significance ★ ⚠ same type
ACTRT2 p.Ala23Val Uncertain significance ★ ⚠ same type
ACTRT2 p.Ala259Gly Uncertain significance ★ ⚠ same type
ACTRT2 p.Ala259Val Uncertain significance ★ ⚠ same type
ACTRT2 p.Ala323Thr 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/actrt2-p-ala361 (accessed [today's date]).

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