Is ACVR1 p.Arg152Cys (c.454C>T) pathogenic?

ACVR1 p.Arg152Cys (c.454C>T) is classified Uncertain significance in ACVR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-12). AlphaMissense: likely benign (0.1239); Very rare (popmax 0.00534%, afr).

How common is ACVR1 p.Arg152Cys (c.454C>T) in the general population?

ACVR1 p.Arg152Cys (c.454C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about ACVR1 p.Arg152Cys (c.454C>T)?

AlphaMissense predicts likely benign (score 0.1239) — an in-silico prediction, not a clinical call.

ACVR1 p.Arg152Cys

c.454C>T · rs771363719 · VCV2920390

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1239 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1239	likely benign
REVEL	0.54	indeterminate
SaProt	LLR -10.21	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 25 kb · p 0.034 · regional, not allelic
Overall
CADD	28.3	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 0.00534% African / African-American · 4/74,852 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000806% 13/1,613,882 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,713
East Asian	0.00446%	22,446
South Asian	0.0022%	45,535
European (non-Finnish)	0.000424%	236,000

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: ACVR1
Protein: p.Arg152Cys
Coding: c.454C>T
MANE Select: NM_001111067
dbSNP: rs771363719
Type: single nucleotide variant
Location: chr2:157778220 (GRCh38)
Gene constraint: LOEUF 0.835 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.70 · 85 PDB

Full ACVR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACVR1 p.Arg152His Uncertain significance ★ ⚠ same residue
ACVR1 p.Arg206His Pathogenic ★★ same type
ACVR1 p.Gly328Glu Pathogenic/Likely pathogenic ★★ same type
ACVR1 p.Gly356Asp Pathogenic/Likely pathogenic ★★ same type
ACVR1 p.Ala134Thr Uncertain significance ★★ ⚠ same type
ACVR1 p.Arg147Gln Uncertain significance ★★ ⚠ same type
ACVR1 p.Arg160Ter Uncertain significance ★★ same type
ACVR1 p.Arg307Gln 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/acvr1-p-arg152cys (accessed [today's date]).

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