Is ACTRT1 p.Asn292Ser (c.875A>G) pathogenic?

ACTRT1 p.Asn292Ser (c.875A>G) is classified Benign in ACTRT1 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-03-29). AlphaMissense: likely benign (0.0784); Low-frequency (popmax 2.32%, sas).

How common is ACTRT1 p.Asn292Ser (c.875A>G) in the general population?

ACTRT1 p.Asn292Ser (c.875A>G) is low-frequency (popmax 2.32%, sas) (gnomAD).

What do computational predictors say about ACTRT1 p.Asn292Ser (c.875A>G)?

AlphaMissense predicts likely benign (score 0.0784) — an in-silico prediction, not a clinical call.

ACTRT1 p.Asn292Ser

c.875A>G · rs144040239 · VCV714567

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0784 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.32%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0784	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -4.81	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 -0.041
Regional constraint	o/e 1.15	unconstrained · MANE · 1,127 bp · p 0.013 · regional, not allelic
Overall
CADD	3.747	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 2.32% South Asian · 1,312/56,574 alleles

Filtering AF 2.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.17%

Overall 0.179% 2,165/1,207,846 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.32%	43
East Asian	1.69%	59
Remaining individualsnot grpmax-eligible	0.242%	414
Ashkenazi Jewishnot grpmax-eligible	0.0182%	5,502
European (non-Finnish)	0.0174%	5,736
African / African-American	0.0106%	9,422
Admixed American	0.00881%	11,356

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.Asn292Ser
Coding: c.875A>G
MANE Select: NM_138289
dbSNP: rs144040239
Type: single nucleotide variant
Location: chrX:128051332 (GRCh38)
Structure: AlphaFold pLDDT 92.94
Residue 292: 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-asn292ser (accessed [today's date]).

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