Is DHH p.Cys343Arg (c.1027T>C) pathogenic?

DHH p.Cys343Arg (c.1027T>C) is classified Likely pathogenic in DHH (ClinVar, Single submitter, 1 submitter; last evaluated 2016-09-08). AlphaMissense: likely pathogenic (0.9902); Absent from gnomAD v4.1; Associated with 46,XY sex reversal 7.

What condition is associated with DHH p.Cys343Arg (c.1027T>C)?

DHH p.Cys343Arg (c.1027T>C) is associated with 46,XY sex reversal 7 (ClinVar).

How common is DHH p.Cys343Arg (c.1027T>C) in the general population?

DHH p.Cys343Arg (c.1027T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHH p.Cys343Arg (c.1027T>C)?

AlphaMissense predicts likely pathogenic (score 0.9902) — an in-silico prediction, not a clinical call.

DHH p.Cys343Arg

c.1027T>C · rs867798393 · VCV265768

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9902 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,556,996)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

46,XY sex reversal 7

Computational evidence

Protein change
AlphaMissense	0.9902	likely pathogenic ✓ concordant with ClinVar · top 8% in DHH
REVEL	0.915	moderately pathogenic-leaning
SaProt	LLR -13.77	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 11	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	32.0	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

No allele count reported in gnomAD v4.1 (AN 1,556,996). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DHH
Protein: p.Cys343Arg
Coding: c.1027T>C
MANE Select: NM_021044
dbSNP: rs867798393
Type: single nucleotide variant
Location: chr12:49090023 (GRCh38)
Gene constraint: LOEUF 0.999 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 5 PDB
Residue 343: 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-cys343arg (accessed [today's date]).

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