Is DEAF1 p.Phe240Ser (c.719T>C) pathogenic?

DEAF1 p.Phe240Ser (c.719T>C) is classified Pathogenic in DEAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-08). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with intellectual disability, autosomal dominant 24.

What condition is associated with DEAF1 p.Phe240Ser (c.719T>C)?

DEAF1 p.Phe240Ser (c.719T>C) is associated with intellectual disability, autosomal dominant 24 (ClinVar).

How common is DEAF1 p.Phe240Ser (c.719T>C) in the general population?

DEAF1 p.Phe240Ser (c.719T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DEAF1 p.Phe240Ser (c.719T>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

DEAF1 p.Phe240Ser

c.719T>C · rs2133402508 · VCV1342716

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, autosomal dominant 24

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar · top 4% in DEAF1
REVEL	0.741	pathogenic-leaning
SaProt	LLR -16.33	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 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 6,629 bp · p 2.3e-11 · regional, not allelic
Overall
CADD	28.3	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.Phe240Ser
Coding: c.719T>C
MANE Select: NM_021008
dbSNP: rs2133402508
Type: single nucleotide variant
Location: chr11:686943 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.62 · 3 PDB
Residue 240: the sand domain

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.Phe240= Likely benign ★★ same residue
DEAF1 p.Phe240Ile Likely pathogenic ★ 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-phe240ser (accessed [today's date]).

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