Is DEAF1 p.Pro299Ser (c.895C>T) pathogenic?

DEAF1 p.Pro299Ser (c.895C>T) is classified Uncertain significance in DEAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-19). AlphaMissense: likely pathogenic (0.9948); Absent from gnomAD v4.1.

How common is DEAF1 p.Pro299Ser (c.895C>T) in the general population?

DEAF1 p.Pro299Ser (c.895C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DEAF1 p.Pro299Ser (c.895C>T)?

AlphaMissense predicts likely pathogenic (score 0.9948) — an in-silico prediction, not a clinical call.

DEAF1 p.Pro299Ser

c.895C>T · rs2494418211 · VCV2767393

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9948 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9948	likely pathogenic · top 10% in DEAF1
REVEL	0.665	pathogenic-leaning
SaProt	LLR -10.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.49	acceptor gain · deltas
Pangolin	Δ0.38	gain · loss 0.32 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 40 kb · p 0.059 · regional, not allelic
Overall
CADD	33.0	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.Pro299Ser
Coding: c.895C>T
MANE Select: NM_021008
dbSNP: rs2494418211
Type: single nucleotide variant
Location: chr11:681065 (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

Similar variants

DEAF1 p.Pro299= Likely benign ★ 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
DEAF1 p.Arg351Ter 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-pro299ser (accessed [today's date]).

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