Is DHH p.Glu64= (c.192G>A) pathogenic?

DHH p.Glu64= (c.192G>A) is classified Benign in DHH (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-15). Rare (popmax 0.347%, amr); Associated with 46,XY sex reversal 7.

What condition is associated with DHH p.Glu64= (c.192G>A)?

DHH p.Glu64= (c.192G>A) is associated with 46,XY sex reversal 7 (ClinVar).

How common is DHH p.Glu64= (c.192G>A) in the general population?

DHH p.Glu64= (c.192G>A) is rare (popmax 0.347%, amr) (gnomAD).

DHH p.Glu64=

c.192G>A · rs201464596 · VCV775008

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.347%, amr)

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 1.1	GERP -0.65, phastCons 1
Overall
CADD	7.517	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.347% Admixed American · 208/60,024 alleles

Filtering AF 0.308% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.293%

Overall 0.0138% 223/1,613,338 alleles · rare exomes 202/1,460,974 · genomes 21/152,364 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.347%	289
East Asian	0.0223%	4,488
Remaining individualsnot grpmax-eligible	0.0064%	15,626
European (non-Finnish)	8.47e-05%	1,179,947

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.Glu64=
Coding: c.192G>A
MANE Select: NM_021044
dbSNP: rs201464596
Type: single nucleotide variant
Location: chr12:49094321 (GRCh38)
Gene constraint: LOEUF 0.999 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 5 PDB

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-glu64 (accessed [today's date]).

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