Is DHH p.Pro201Gln (c.602C>A) pathogenic?

DHH p.Pro201Gln (c.602C>A) is classified Uncertain significance in DHH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-15). AlphaMissense: likely pathogenic (0.9445); Very rare (popmax 0.00223%, eas); Associated with 46,XY sex reversal 7.

What condition is associated with DHH p.Pro201Gln (c.602C>A)?

DHH p.Pro201Gln (c.602C>A) is associated with 46,XY sex reversal 7 (ClinVar).

How common is DHH p.Pro201Gln (c.602C>A) in the general population?

DHH p.Pro201Gln (c.602C>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DHH p.Pro201Gln (c.602C>A)?

AlphaMissense predicts likely pathogenic (score 0.9445) — an in-silico prediction, not a clinical call.

DHH p.Pro201Gln

c.602C>A · rs2498533397 · VCV2966235

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9445 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

46,XY sex reversal 7

Computational evidence

Protein change
AlphaMissense	0.9445	likely pathogenic
REVEL	0.876	moderately pathogenic-leaning
SaProt	LLR -13.82	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 12	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	29.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,848 alleles

Overall 6.88e-05% 1/1,454,372 alleles · very rare

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: DHH
Protein: p.Pro201Gln
Coding: c.602C>A
MANE Select: NM_021044
dbSNP: rs2498533397
Type: single nucleotide variant
Location: chr12:49090448 (GRCh38)
Gene constraint: LOEUF 0.999 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 5 PDB
Residue 201: 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

46,XY sex reversal 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHH c.*401G>T Uncertain significance ★★ same condition
DHH p.Ala287Glu Uncertain significance ★★ ⚠ same condition
DHH p.Arg102His Uncertain significance ★★ ⚠ same condition
DHH p.Arg309Leu Uncertain significance ★★ ⚠ same condition
DHH p.Arg318Pro Uncertain significance ★★ ⚠ same condition
DHH p.Ser210Arg Uncertain significance ★★ ⚠ same condition
DHH c.304-15T>C Likely benign ★★ same condition
DHH c.-255T>C Benign ★★ 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/dhh-p-pro201gln (accessed [today's date]).

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