Is DEAF1 p.Ala71Pro (c.211G>C) pathogenic?

DEAF1 p.Ala71Pro (c.211G>C) is classified Uncertain significance in DEAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-02). AlphaMissense: likely benign (0.2086); Very rare (popmax 0.00314%, nfe).

How common is DEAF1 p.Ala71Pro (c.211G>C) in the general population?

DEAF1 p.Ala71Pro (c.211G>C) is very rare (popmax 0.00314%, nfe) (gnomAD).

What do computational predictors say about DEAF1 p.Ala71Pro (c.211G>C)?

AlphaMissense predicts likely benign (score 0.2086) — an in-silico prediction, not a clinical call.

DEAF1 p.Ala71Pro

c.211G>C · rs778253261 · VCV1505467

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2086 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2086	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -7.15	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 2.9	GERP 0.85, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 3,508 bp · p 0.014 · regional, not allelic
Overall
CADD	23.6	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

Grpmax group 0.00314% European (non-Finnish) · 35/1,114,904 alleles

Filtering AF 0.00228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00265% 35/1,319,060 alleles · very rare

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.Ala71Pro
Coding: c.211G>C
MANE Select: NM_021008
dbSNP: rs778253261
Type: single nucleotide variant
Location: chr11:694837 (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.Ala71_Glu72insMetAlaAla Uncertain significance ★ 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-ala71pro (accessed [today's date]).

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