Is DHH p.Phe242= (c.726C>T) pathogenic?

DHH p.Phe242= (c.726C>T) is classified Uncertain significance in DHH (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 8.5e-05%, nfe); Associated with 46,XY sex reversal 7.

What condition is associated with DHH p.Phe242= (c.726C>T)?

DHH p.Phe242= (c.726C>T) is associated with 46,XY sex reversal 7 (ClinVar).

How common is DHH p.Phe242= (c.726C>T) in the general population?

DHH p.Phe242= (c.726C>T) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

DHH p.Phe242=

c.726C>T · rs886049491 · VCV309100

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Conditions

46,XY sex reversal 7

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 2.5	GERP -4.9, phastCons 1
Overall
CADD	16.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,176,736 alleles

Overall 0.000657% 1/152,244 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.Phe242=
Coding: c.726C>T
MANE Select: NM_021044
dbSNP: rs886049491
Type: single nucleotide variant
Location: chr12:49090324 (GRCh38)
Gene constraint: LOEUF 0.999 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 5 PDB
Residue 242: 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-phe242 (accessed [today's date]).

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