Is DEAF1 p.Pro73Ser (c.217C>T) pathogenic?

DEAF1 p.Pro73Ser (c.217C>T) is classified Conflicting classifications of pathogenicity in DEAF1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-06-12). AlphaMissense: likely benign (0.0807); Ultra-rare (popmax 0.0239%, mid); Associated with Inborn genetic diseases.

What condition is associated with DEAF1 p.Pro73Ser (c.217C>T)?

DEAF1 p.Pro73Ser (c.217C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DEAF1 p.Pro73Ser (c.217C>T) in the general population?

DEAF1 p.Pro73Ser (c.217C>T) is ultra-rare (popmax 0.0239%, mid) (gnomAD).

What do computational predictors say about DEAF1 p.Pro73Ser (c.217C>T)?

AlphaMissense predicts likely benign (score 0.0807) — an in-silico prediction, not a clinical call.

DEAF1 p.Pro73Ser

c.217C>T · rs1243122062 · VCV1488957

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0807 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0239%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0807	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -6.40	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 2.4	GERP -1.6, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 3,508 bp · p 0.014 · regional, not allelic
Overall
CADD	18.88	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 0.0239% Middle Eastern · 1/4,182 alleles

Filtering AF 0.000132% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.6e-05%

Overall 0.000411% 6/1,460,554 alleles · ultra-rare exomes 6/1,309,116 · genomes 0/151,438 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0239%	4,182
European (non-Finnish)	0.00045%	221,982

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.Pro73Ser
Coding: c.217C>T
MANE Select: NM_021008
dbSNP: rs1243122062
Type: single nucleotide variant
Location: chr11:694831 (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.Pro73= Likely benign ★★ same residue
DEAF1 p.Pro73Thr Uncertain significance ★ ⚠ 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.Ala26Val 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-pro73ser (accessed [today's date]).

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