Is ACVR1C p.Ile293Ser (c.878T>G) pathogenic?

ACVR1C p.Ile293Ser (c.878T>G) is classified Uncertain significance in ACVR1C (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-30). AlphaMissense: likely benign (0.2549); Ultra-rare (popmax 0.0356%, eas).

How common is ACVR1C p.Ile293Ser (c.878T>G) in the general population?

ACVR1C p.Ile293Ser (c.878T>G) is ultra-rare (popmax 0.0356%, eas) (gnomAD).

What do computational predictors say about ACVR1C p.Ile293Ser (c.878T>G)?

AlphaMissense predicts likely benign (score 0.2549) — an in-silico prediction, not a clinical call.

ACVR1C p.Ile293Ser

c.878T>G · rs116070910 · VCV2206204

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2549 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0356%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2549	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -10.72	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.5, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 95 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	25.0	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 0.0356% East Asian · 16/44,882 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.0013% 21/1,614,132 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0356%	2,805
South Asian	0.00549%	18,216

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: ACVR1C
Protein: p.Ile293Ser
Coding: c.878T>G
MANE Select: NM_145259
dbSNP: rs116070910
Type: single nucleotide variant
Location: chr2:157544510 (GRCh38)
Gene constraint: LOEUF 0.6 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 85.35
Residue 293: the protein kinase domain

Full ACVR1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACVR1C c.1226-50T>C Benign ★★ same type
ACVR1C c.1356+6G>C Benign ★★ same type
ACVR1C c.305-34T>C Benign ★★ same type
ACVR1C c.544+63A>G Benign ★★ same type
ACVR1C c.73+9C>A Benign ★★ same type
ACVR1C c.776-13A>G Benign ★★ same type
ACVR1C c.943+49G>A Benign ★★ same type
ACVR1C p.Asn150His Benign ★★ 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/acvr1c-p-ile293ser (accessed [today's date]).

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