Is GDF5 p.Ala261= (c.783C>G) pathogenic?

GDF5 p.Ala261= (c.783C>G) is classified Likely benign in GDF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-27). AlphaMissense: likely pathogenic (0.6674); Absent from gnomAD v4.1.

How common is GDF5 p.Ala261= (c.783C>G) in the general population?

GDF5 p.Ala261= (c.783C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GDF5 p.Ala261= (c.783C>G)?

AlphaMissense predicts likely pathogenic (score 0.6674) — an in-silico prediction, not a clinical call.

GDF5 p.Ala261=

c.783C>G · rs2515420879 · VCV2836153

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6674 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6674	likely pathogenic
REVEL	0.228	benign-leaning
SaProt	LLR -6.51	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 12	GERP 1.7, phastCons 1
Overall
CADD	20.2	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: GDF5
Protein: p.Ala261=
Coding: c.783C>G
MANE Select: NM_000557
dbSNP: rs2515420879
Type: single nucleotide variant
Location: chr20:35434632 (GRCh38)
Gene constraint: LOEUF 0.71 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.04 · 15 PDB
Residue 261: the 'disordered' region

Full GDF5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GDF5 p.Arg156Ter Pathogenic/Likely pathogenic ★★ same type
GDF5 p.Arg301Ter Pathogenic/Likely pathogenic ★★ ⚠ same type
GDF5 p.Arg380Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
GDF5 p.Cys400Tyr Likely pathogenic ★★ same type
GDF5 p.Gln210Ter Pathogenic/Likely pathogenic ★★ same type
GDF5 p.Glu491Lys Pathogenic ★★ ⚠ same type
GDF5 p.Trp297Ter Pathogenic/Likely pathogenic ★★ same type
GDF5 p.Ala254Asp 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/gdf5-p-ala261 (accessed [today's date]).

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