Is ACVR1 p.Phe71Leu (c.211T>C) pathogenic?

ACVR1 p.Phe71Leu (c.211T>C) is classified Uncertain significance in ACVR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-17). AlphaMissense: likely pathogenic (0.9741); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACVR1 p.Phe71Leu (c.211T>C)?

ACVR1 p.Phe71Leu (c.211T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ACVR1 p.Phe71Leu (c.211T>C) in the general population?

ACVR1 p.Phe71Leu (c.211T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACVR1 p.Phe71Leu (c.211T>C)?

AlphaMissense predicts likely pathogenic (score 0.9741) — an in-silico prediction, not a clinical call.

ACVR1 p.Phe71Leu

c.211T>C · rs2467967384 · VCV2277547

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9741 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9741	likely pathogenic
REVEL	0.29	benign-leaning
SaProt	LLR -7.74	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 25 kb · p 0.034 · regional, not allelic
Overall
CADD	23.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACVR1
Protein: p.Phe71Leu
Coding: c.211T>C
MANE Select: NM_001111067
dbSNP: rs2467967384
Type: single nucleotide variant
Location: chr2:157780457 (GRCh38)
Gene constraint: LOEUF 0.835 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.70 · 85 PDB
Residue 71: a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACVR1 p.Gly328Glu Pathogenic/Likely pathogenic ★★ same condition
ACVR1 p.Arg147Gln Uncertain significance ★★ ⚠ same condition
ACVR1 p.Arg307Gln Uncertain significance ★★ ⚠ same condition
ACVR1 p.Arg417Gln Uncertain significance ★★ ⚠ same condition
ACVR1 p.Gly39Val Uncertain significance ★★ ⚠ same condition
ACVR1 p.His121Tyr Uncertain significance ★★ ⚠ same condition
ACVR1 p.Ile236Leu Uncertain significance ★★ ⚠ same condition
ACVR1 p.Ile352Val Uncertain significance ★★ ⚠ same condition

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-phe71leu (accessed [today's date]).

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