Is DEAF1 p.Ala276Pro (c.826G>C) pathogenic?

DEAF1 p.Ala276Pro (c.826G>C) is classified Pathogenic in DEAF1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2020-06-02). AlphaMissense: likely pathogenic (0.9939); Absent from gnomAD v4.1; Associated with intellectual disability, autosomal dominant 24.

What condition is associated with DEAF1 p.Ala276Pro (c.826G>C)?

DEAF1 p.Ala276Pro (c.826G>C) is associated with intellectual disability, autosomal dominant 24 (ClinVar).

How common is DEAF1 p.Ala276Pro (c.826G>C) in the general population?

DEAF1 p.Ala276Pro (c.826G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DEAF1 p.Ala276Pro (c.826G>C)?

AlphaMissense predicts likely pathogenic (score 0.9939) — an in-silico prediction, not a clinical call.

DEAF1 p.Ala276Pro

c.826G>C · rs1383819913 · VCV915950

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9939 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual disability, autosomal dominant 24

Computational evidence

Protein change
AlphaMissense	0.9939	likely pathogenic ✓ concordant with ClinVar
REVEL	0.585	indeterminate
SaProt	LLR -8.78	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.5, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 6,629 bp · p 2.3e-11 · regional, not allelic
Overall
CADD	27.2	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: DEAF1
Protein: p.Ala276Pro
Coding: c.826G>C
MANE Select: NM_021008
dbSNP: rs1383819913
Type: single nucleotide variant
Location: chr11:684942 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.62 · 3 PDB

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

Disease context

intellectual disability, autosomal dominant 24 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DEAF1 p.Ala276Val Uncertain significance ★ ⚠ same residue
DEAF1 p.Ala276Thr Uncertain significance ★★ ⚠ same residue
DEAF1 p.Arg224Pro Pathogenic/Likely pathogenic ★★ same condition
DEAF1 p.Arg224Trp Pathogenic/Likely pathogenic ★★ same condition
DEAF1 p.Arg246Thr Pathogenic/Likely pathogenic ★★ same condition
DEAF1 p.Cys281Ser Likely pathogenic ★★ same condition
DEAF1 p.Gly212Ser Pathogenic/Likely pathogenic ★★ same condition
DEAF1 p.Lys250Glu Pathogenic/Likely 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/deaf1-p-ala276pro (accessed [today's date]).

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