Is DHH p.Arg245Pro (c.734G>C) pathogenic?

DHH p.Arg245Pro (c.734G>C) is classified Likely pathogenic in DHH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely pathogenic (0.9399); Absent from gnomAD v4.1; Associated with Differences in sex development.

What condition is associated with DHH p.Arg245Pro (c.734G>C)?

DHH p.Arg245Pro (c.734G>C) is associated with Differences in sex development (ClinVar).

How common is DHH p.Arg245Pro (c.734G>C) in the general population?

DHH p.Arg245Pro (c.734G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHH p.Arg245Pro (c.734G>C)?

AlphaMissense predicts likely pathogenic (score 0.9399) — an in-silico prediction, not a clinical call.

DHH p.Arg245Pro

c.734G>C · VCV4281674

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9399 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Differences in sex development

Computational evidence

Protein change
AlphaMissense	0.9399	likely pathogenic ✓ concordant with ClinVar
REVEL	0.742	pathogenic-leaning
SaProt	LLR -15.51	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 4,650 bp · p 8.5e-08 · regional, not allelic
Overall
CADD	26.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DHH
Protein: p.Arg245Pro
Coding: c.734G>C
MANE Select: NM_021044
Type: single nucleotide variant
Location: chr12:49090316 (GRCh38)
Gene constraint: LOEUF 0.999 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 5 PDB
Residue 245: a UniProt-annotated variant site (in gdmn; uncertain significance); a UniProt-annotated variant site (in gdmn)

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

Disease context

Differences in sex development

Similar variants

DHH p.Ala227Val Pathogenic ★ ⚠ same condition
DHH p.Thr268Ala Likely pathogenic ★ same condition
DHH p.Trp118Cys Uncertain significance ★ same condition
DHH c.566-2A>G Likely pathogenic same condition
DHH p.Cys199Tyr Uncertain significance ⚠ same condition
DHH c.*401G>T Uncertain significance ★★ same type
DHH p.Ala287Glu Uncertain significance ★★ ⚠ same type
DHH p.Arg102His Uncertain significance ★★ ⚠ 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/dhh-p-arg245pro (accessed [today's date]).

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