Is DHH p.Leu40Pro (c.119T>C) pathogenic?

DHH p.Leu40Pro (c.119T>C) is classified Uncertain significance in DHH (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.1615); Absent from gnomAD v4.1; Associated with 46,XY sex reversal 7.

What condition is associated with DHH p.Leu40Pro (c.119T>C)?

DHH p.Leu40Pro (c.119T>C) is associated with 46,XY sex reversal 7 (ClinVar).

How common is DHH p.Leu40Pro (c.119T>C) in the general population?

DHH p.Leu40Pro (c.119T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHH p.Leu40Pro (c.119T>C)?

AlphaMissense predicts likely benign (score 0.1615) — an in-silico prediction, not a clinical call.

DHH p.Leu40Pro

c.119T>C · rs2498544169 · VCV2572517

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1615 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

46,XY sex reversal 7

Computational evidence

Protein change
AlphaMissense	0.1615	likely benign
REVEL	0.905	moderately pathogenic-leaning
SaProt	LLR -8.25	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.3, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 4,650 bp · p 8.5e-08 · regional, not allelic
Overall
CADD	27.9	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.Leu40Pro
Coding: c.119T>C
MANE Select: NM_021044
dbSNP: rs2498544169
Type: single nucleotide variant
Location: chr12:49094394 (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-leu40pro (accessed [today's date]).

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