Is DEAF1 p.Pro40Arg (c.119C>G) pathogenic?

DEAF1 p.Pro40Arg (c.119C>G) is classified Uncertain significance in DEAF1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-22). AlphaMissense: likely benign (0.1942); No allele count reported in gnomAD v4.1 (AN 1,374,016); Associated with Inborn genetic diseases.

What condition is associated with DEAF1 p.Pro40Arg (c.119C>G)?

DEAF1 p.Pro40Arg (c.119C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DEAF1 p.Pro40Arg (c.119C>G) in the general population?

DEAF1 p.Pro40Arg (c.119C>G) is no allele count reported in gnomAD v4.1 (AN 1,374,016) (gnomAD).

What do computational predictors say about DEAF1 p.Pro40Arg (c.119C>G)?

AlphaMissense predicts likely benign (score 0.1942) — an in-silico prediction, not a clinical call.

DEAF1 p.Pro40Arg

c.119C>G · rs1861044984 · VCV1498388

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1942 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,374,016)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1942	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -6.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 0.8, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 3,508 bp · p 0.014 · regional, not allelic
Overall
CADD	25.0	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 1,374,016). 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: DEAF1
Protein: p.Pro40Arg
Coding: c.119C>G
MANE Select: NM_021008
dbSNP: rs1861044984
Type: single nucleotide variant
Location: chr11:694929 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.62 · 3 PDB
Residue 40: the 'disordered' region

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.Pro40Leu Uncertain significance ★ ⚠ same residue
TMEM80 p.Met40Val Uncertain significance ★ same residue
DEAF1 p.Pro40= 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

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-pro40arg (accessed [today's date]).

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