Is ACVR1 p.Pro19Ser (c.55C>T) pathogenic?

ACVR1 p.Pro19Ser (c.55C>T) is classified Uncertain significance in ACVR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). AlphaMissense: likely benign (0.0682); Very rare (popmax 0.00334%, amr).

How common is ACVR1 p.Pro19Ser (c.55C>T) in the general population?

ACVR1 p.Pro19Ser (c.55C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about ACVR1 p.Pro19Ser (c.55C>T)?

AlphaMissense predicts likely benign (score 0.0682) — an in-silico prediction, not a clinical call.

ACVR1 p.Pro19Ser

c.55C>T · rs1158969294 · VCV1922454

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0682 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0682	likely benign
REVEL	0.346	indeterminate
SaProt	LLR -4.94	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 25 kb · p 0.034 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,952 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000372% 6/1,611,432 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,976
European (non-Finnish)	0.00034%	294,546

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.Pro19Ser
Coding: c.55C>T
MANE Select: NM_001111067
dbSNP: rs1158969294
Type: single nucleotide variant
Location: chr2:157799439 (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.Pro19Ala Uncertain significance ★ ⚠ same residue
ACVR1 p.Pro19Leu Uncertain significance ★ ⚠ same residue
ACVR1 p.Pro19= Likely benign ★ 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

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-pro19ser (accessed [today's date]).

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