Is GDF1 p.Arg271Pro (c.812G>C) pathogenic?

GDF1 p.Arg271Pro (c.812G>C) is classified Uncertain significance in GDF1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-10). AlphaMissense: likely benign (0.2138); No allele count reported in gnomAD v4.1 (AN 1,386,646); Associated with congenital heart defects, multiple types, 6.

What condition is associated with GDF1 p.Arg271Pro (c.812G>C)?

GDF1 p.Arg271Pro (c.812G>C) is associated with congenital heart defects, multiple types, 6 (ClinVar).

How common is GDF1 p.Arg271Pro (c.812G>C) in the general population?

GDF1 p.Arg271Pro (c.812G>C) is no allele count reported in gnomAD v4.1 (AN 1,386,646) (gnomAD).

What do computational predictors say about GDF1 p.Arg271Pro (c.812G>C)?

AlphaMissense predicts likely benign (score 0.2138) — an in-silico prediction, not a clinical call.

GDF1 p.Arg271Pro

c.812G>C · rs2055905199 · VCV966764

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2138 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,386,646)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

congenital heart defects, multiple types, 6

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2138	likely benign
REVEL	0.33	indeterminate
SaProt	LLR -6.76	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.5	GERP -4, phastCons 0.98
Regional constraint	o/e 1.04	unconstrained · MANE · 1,707 bp · p 0.34 · regional, not allelic
Overall
CADD	24.8	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

No allele count reported in gnomAD v4.1 (AN 1,386,646). 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: GDF1
Protein: p.Arg271Pro
Coding: c.812G>C
MANE Select: NM_001492
dbSNP: rs2055905199
Type: single nucleotide variant
Location: chr19:18868904 (GRCh38)

Full GDF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital heart defects, multiple types, 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/gdf1-p-arg271pro (accessed [today's date]).

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