Is DEAF1 p.Pro84Arg (c.251C>G) pathogenic?

DEAF1 p.Pro84Arg (c.251C>G) is classified Uncertain significance in DEAF1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-09). AlphaMissense: ambiguous (0.3758); Ultra-rare (popmax 0.0769%, mid); Associated with Inborn genetic diseases.

What condition is associated with DEAF1 p.Pro84Arg (c.251C>G)?

DEAF1 p.Pro84Arg (c.251C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DEAF1 p.Pro84Arg (c.251C>G) in the general population?

DEAF1 p.Pro84Arg (c.251C>G) is ultra-rare (popmax 0.0769%, mid) (gnomAD).

What do computational predictors say about DEAF1 p.Pro84Arg (c.251C>G)?

AlphaMissense predicts ambiguous (score 0.3758) — an in-silico prediction, not a clinical call.

DEAF1 p.Pro84Arg

c.251C>G · rs763981738 · VCV2053731

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3758 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0769%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3758	ambiguous
REVEL	0.337	indeterminate
SaProt	LLR -7.72	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.88, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 3,508 bp · p 0.014 · regional, not allelic
Overall
CADD	24.4	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

Grpmax group 0.0769% Middle Eastern · 3/3,902 alleles

Filtering AF 0.0209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0111%

Overall 0.0038% 53/1,395,126 alleles · ultra-rare exomes 45/1,243,508 · genomes 8/151,618 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0769%	1,301
Admixed American	0.0115%	8,708
Remaining individualsnot grpmax-eligible	0.00565%	17,707
European (non-Finnish)	0.00391%	25,607
African / African-American	0.0015%	66,842

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DEAF1
Protein: p.Pro84Arg
Coding: c.251C>G
MANE Select: NM_021008
dbSNP: rs763981738
Type: single nucleotide variant
Location: chr11:694797 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DEAF1 p.Pro84Leu Uncertain significance ★ same residue
DEAF1 p.Pro84= Likely benign ★ same residue
DEAF1 p.Arg226Trp Pathogenic/Likely pathogenic ★★ same condition
DEAF1 p.Ala16Val Uncertain significance ★★ ⚠ same condition
DEAF1 p.Ala18Val Uncertain significance ★★ ⚠ same condition
DEAF1 p.Ala26Val Uncertain significance ★★ ⚠ same condition
DEAF1 p.Ala27Gly Uncertain significance ★★ ⚠ same condition
DEAF1 p.Ala352Thr Uncertain significance ★★ ⚠ 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-pro84arg (accessed [today's date]).

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