Is DIAPH1 p.Phe812= (c.2436C>T) pathogenic?

DIAPH1 p.Phe812= (c.2436C>T) is classified Likely benign in DIAPH1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0427%, afr); Associated with autosomal dominant nonsyndromic hearing loss 1.

What condition is associated with DIAPH1 p.Phe812= (c.2436C>T)?

DIAPH1 p.Phe812= (c.2436C>T) is associated with autosomal dominant nonsyndromic hearing loss 1, progressive microcephaly-seizures-cortical blindness-developmental delay syndrome (ClinVar).

How common is DIAPH1 p.Phe812= (c.2436C>T) in the general population?

DIAPH1 p.Phe812= (c.2436C>T) is ultra-rare (popmax 0.0427%, afr) (gnomAD).

DIAPH1 p.Phe812=

c.2436C>T · rs185113837 · VCV1141951

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0427%, afr)

Conditions

autosomal dominant nonsyndromic hearing loss 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.69	GERP -5.4
Overall
CADD	7.549	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0427% African / African-American · 32/75,028 alleles

Filtering AF 0.031% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0271%

Overall 0.00359% 58/1,614,126 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0427%	2,345
South Asian	0.011%	9,108
East Asian	0.00446%	22,441
Remaining individualsnot grpmax-eligible	0.0032%	31,255
Admixed American	0.00167%	60,022
European (non-Finnish)	0.000932%	107,273

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: DIAPH1
Protein: p.Phe812=
Coding: c.2436C>T
MANE Select: NM_005219
dbSNP: rs185113837
Type: single nucleotide variant
Location: chr5:141571963 (GRCh38)
Gene constraint: LOEUF 0.367 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.04 · 1 PDB
Residue 812: the fh2 domain

Full DIAPH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant nonsyndromic hearing loss 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: progressive microcephaly-seizures-cortical blindness-developmental delay syndrome

Similar variants

DIAPH1 c.145-1G>A Likely pathogenic ★★ same condition
DIAPH1 c.684+1G>A Pathogenic ★★ same condition
DIAPH1 p.Arg1049Ter Pathogenic ★★ same condition
DIAPH1 p.Arg1213Ter Pathogenic ★★ same condition
DIAPH1 p.Arg331Ter Pathogenic ★★ same condition
DIAPH1 p.Arg351Ter Pathogenic ★★ same condition
DIAPH1 p.Gln778Ter Pathogenic/Likely pathogenic ★★ same condition
DIAPH1 c.402+5G>A 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/diaph1-p-phe812 (accessed [today's date]).

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