Is ACVRL1 p.Cys36Phe (c.107G>T) pathogenic?

ACVRL1 p.Cys36Phe (c.107G>T) is classified Uncertain significance in ACVRL1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-25). AlphaMissense: likely pathogenic (0.9401); Absent from gnomAD v4.1; Associated with ACVRL1-related disorder.

What condition is associated with ACVRL1 p.Cys36Phe (c.107G>T)?

ACVRL1 p.Cys36Phe (c.107G>T) is associated with ACVRL1-related disorder (ClinVar).

How common is ACVRL1 p.Cys36Phe (c.107G>T) in the general population?

ACVRL1 p.Cys36Phe (c.107G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACVRL1 p.Cys36Phe (c.107G>T)?

AlphaMissense predicts likely pathogenic (score 0.9401) — an in-silico prediction, not a clinical call.

ACVRL1 p.Cys36Phe

c.107G>T · VCV3346788

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9401 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,607,134)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ACVRL1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9401	likely pathogenic
REVEL	0.887	moderately pathogenic-leaning
SaProt	LLR -12.11	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,260 bp · p 0.091 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,607,134). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACVRL1
Protein: p.Cys36Phe
Coding: c.107G>T
MANE Select: NM_000020
Type: single nucleotide variant
Location: chr12:51913144 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.51 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.77 · 7 PDB
Residue 36: a disulfide bond

Full ACVRL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ACVRL1-related disorder

Similar variants

ACVRL1 p.Cys36Arg Pathogenic ★ same residue
ACVRL1 p.Cys36Tyr Likely pathogenic ★ same residue
ACVRL1 c.313+1G>T Pathogenic ★★ same condition
ACVRL1 c.625+1G>A Pathogenic/Likely pathogenic ★★ same condition
ACVRL1 c.625+2T>C Pathogenic/Likely pathogenic ★★ same condition
ACVRL1 p.Ala306Glu Likely pathogenic ★★ same condition
ACVRL1 p.Ala352Asp Pathogenic/Likely pathogenic ★★ same condition
ACVRL1 p.Arg374Gln Pathogenic ★★ 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/acvrl1-p-cys36phe (accessed [today's date]).

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