Is DEAF1 p.Ala26Val (c.77C>T) pathogenic?

DEAF1 p.Ala26Val (c.77C>T) is classified Uncertain significance in DEAF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-14). AlphaMissense: ambiguous (0.4609); Ultra-rare (popmax 0.0119%, eas); Associated with Inborn genetic diseases.

What condition is associated with DEAF1 p.Ala26Val (c.77C>T)?

DEAF1 p.Ala26Val (c.77C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DEAF1 p.Ala26Val (c.77C>T) in the general population?

DEAF1 p.Ala26Val (c.77C>T) is ultra-rare (popmax 0.0119%, eas) (gnomAD).

What do computational predictors say about DEAF1 p.Ala26Val (c.77C>T)?

AlphaMissense predicts ambiguous (score 0.4609) — an in-silico prediction, not a clinical call.

DEAF1 p.Ala26Val

c.77C>T · rs1428678041 · VCV2102054

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4609 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0119%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4609	ambiguous
REVEL	0.067	moderately benign-leaning
SaProt	LLR -8.00	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 0.83, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 3,508 bp · p 0.014 · regional, not allelic
Overall
CADD	23.2	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 0.0119% East Asian · 2/16,846 alleles

Filtering AF 0.00206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000833%

Overall 0.000646% 6/928,566 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0119%	8,423
South Asian	0.00345%	28,962
European (non-Finnish)	0.00034%	294,215

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.Ala26Val
Coding: c.77C>T
MANE Select: NM_021008
dbSNP: rs1428678041
Type: single nucleotide variant
Location: chr11:694971 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DEAF1 p.Ala26Pro Uncertain significance ★ ⚠ same residue
TMEM80 p.Ser26= Likely benign ★ same residue
DEAF1 p.Ala26= 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.Ala27Gly Uncertain significance ★★ ⚠ same condition
DEAF1 p.Ala352Thr 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-ala26val (accessed [today's date]).

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