Is ACVR1C p.Ser7= (c.21A>G) pathogenic?

ACVR1C p.Ser7= (c.21A>G) is classified Likely benign in ACVR1C (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-11-06). Very rare (popmax 0.00478%, nfe); Associated with ACVR1C-related disorder.

What condition is associated with ACVR1C p.Ser7= (c.21A>G)?

ACVR1C p.Ser7= (c.21A>G) is associated with ACVR1C-related disorder (ClinVar).

How common is ACVR1C p.Ser7= (c.21A>G) in the general population?

ACVR1C p.Ser7= (c.21A>G) is very rare (popmax 0.00478%, nfe) (gnomAD).

ACVR1C p.Ser7=

c.21A>G · rs777827727 · VCV3037015

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00478%, nfe)

Conditions

ACVR1C-related disorder

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 -0.15	GERP -0.23, phastCons 0.005
Overall
CADD	11.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00478% European (non-Finnish) · 56/1,171,884 alleles

Filtering AF 0.00377% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00339%

Overall 0.00357% 57/1,594,872 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00478%	20,926
East Asian	0.00228%	43,872

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.Ser7=
Coding: c.21A>G
MANE Select: NM_145259
dbSNP: rs777827727
Type: single nucleotide variant
Location: chr2:157628624 (GRCh38)
Gene constraint: LOEUF 0.6 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 85.35

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

Disease context

ACVR1C-related disorder

Similar variants

ACVR1C c.943+4T>C Benign same condition
ACVR1C p.Ala340= Benign same condition
ACVR1C p.Asn150= Benign same condition
ACVR1C p.Ile195Thr Likely benign same condition
ACVR1C p.Val487Ile Benign same condition
ACVR1C c.1226-50T>C Benign ★★ same type
ACVR1C c.1356+6G>C Benign ★★ same type
ACVR1C c.305-34T>C 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-ser7 (accessed [today's date]).

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