Is DEAF1 p.Ala7Val (c.20C>T) pathogenic?

DEAF1 p.Ala7Val (c.20C>T) is classified Uncertain significance in DEAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). AlphaMissense: likely pathogenic (0.7549); Very rare (popmax 0.000186%, nfe).

How common is DEAF1 p.Ala7Val (c.20C>T) in the general population?

DEAF1 p.Ala7Val (c.20C>T) is very rare (popmax 0.000186%, nfe) (gnomAD).

What do computational predictors say about DEAF1 p.Ala7Val (c.20C>T)?

AlphaMissense predicts likely pathogenic (score 0.7549) — an in-silico prediction, not a clinical call.

DEAF1 p.Ala7Val

c.20C>T · VCV3649138

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7549 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000186%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7549	likely pathogenic
REVEL	0.125	moderately benign-leaning
SaProt	LLR -7.41	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 0.85, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 3,508 bp · p 0.014 · regional, not allelic
Overall
CADD	25.1	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 0.000186% European (non-Finnish) · 2/1,077,000 alleles

Filtering AF 3.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2e-05%

Overall 0.000142% 2/1,406,334 alleles · very rare exomes 2/1,254,794 · genomes 0/151,540 · joint denominator

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.Ala7Val
Coding: c.20C>T
MANE Select: NM_021008
Type: single nucleotide variant
Location: chr11:695028 (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.Ala7= 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-ala7val (accessed [today's date]).

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