Is DHH p.Arg156Pro (c.467G>C) pathogenic?

DHH p.Arg156Pro (c.467G>C) is classified Uncertain significance in DHH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: ambiguous (0.4139); Very rare (popmax 0.000763%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DHH p.Arg156Pro (c.467G>C)?

DHH p.Arg156Pro (c.467G>C) is associated with Inborn genetic diseases (ClinVar).

How common is DHH p.Arg156Pro (c.467G>C) in the general population?

DHH p.Arg156Pro (c.467G>C) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about DHH p.Arg156Pro (c.467G>C)?

AlphaMissense predicts ambiguous (score 0.4139) — an in-silico prediction, not a clinical call.

DHH p.Arg156Pro

c.467G>C · VCV4239998

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4139 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4139	ambiguous
REVEL	0.808	moderately pathogenic-leaning
SaProt	LLR -8.90	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	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	31.0	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

Grpmax group 0.000763% European (non-Finnish) · 9/1,180,038 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,614,236 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.Arg156Pro
Coding: c.467G>C
MANE Select: NM_021044
Type: single nucleotide variant
Location: chr12:49091226 (GRCh38)
Gene constraint: LOEUF 0.999 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 5 PDB
Residue 156: an α-helix

Full DHH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHH p.Arg102His Uncertain significance ★★ ⚠ same condition
DHH p.Ala193Val Uncertain significance ★ ⚠ same condition
DHH p.Ala291Thr Uncertain significance ★ ⚠ same condition
DHH p.Ala36Ser Uncertain significance ★ ⚠ same condition
DHH p.Arg102Cys Uncertain significance ★ ⚠ same condition
DHH p.Arg106Gln Uncertain significance ★ ⚠ same condition
DHH p.Arg179Cys Uncertain significance ★ ⚠ same condition
DHH p.Arg277Pro Uncertain significance ★ ⚠ 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-arg156pro (accessed [today's date]).

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