Is DEAF1 p.Arg509Pro (c.1526G>C) pathogenic?

DEAF1 p.Arg509Pro (c.1526G>C) is classified Uncertain significance in DEAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-31). AlphaMissense: likely pathogenic (0.997); Absent from gnomAD v4.1.

How common is DEAF1 p.Arg509Pro (c.1526G>C) in the general population?

DEAF1 p.Arg509Pro (c.1526G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DEAF1 p.Arg509Pro (c.1526G>C)?

AlphaMissense predicts likely pathogenic (score 0.997) — an in-silico prediction, not a clinical call.

DEAF1 p.Arg509Pro

c.1526G>C · VCV3602387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.997	likely pathogenic · top 9% in DEAF1
REVEL	0.697	pathogenic-leaning
SaProt	LLR -16.66	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 7.3	GERP 1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 40 kb · p 0.059 · regional, not allelic
Overall
CADD	29.3	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

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: DEAF1
Protein: p.Arg509Pro
Coding: c.1526G>C
MANE Select: NM_021008
Type: single nucleotide variant
Location: chr11:654029 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.62 · 3 PDB
Residue 509: a β-strand

Full DEAF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DEAF1 p.Arg509Gln Uncertain significance ★★ ⚠ same residue
DEAF1 p.Arg509Trp Uncertain significance ★★ ⚠ same residue
DEAF1 c.998-2A>G Likely pathogenic ★★ same type
DEAF1 p.Arg224Pro Pathogenic/Likely pathogenic ★★ same type
DEAF1 p.Arg224Trp Pathogenic/Likely pathogenic ★★ same type
DEAF1 p.Arg226Trp Pathogenic/Likely pathogenic ★★ same type
DEAF1 p.Arg246Thr Pathogenic/Likely pathogenic ★★ same type
DEAF1 p.Arg261Ter Pathogenic/Likely pathogenic ★★ 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/deaf1-p-arg509pro (accessed [today's date]).

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