Is DHH p.Ala193Val (c.578C>T) pathogenic?

DHH p.Ala193Val (c.578C>T) is classified Uncertain significance in DHH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely benign (0.276); Very rare (popmax 0.0033%, sas); Associated with Inborn genetic diseases.

What condition is associated with DHH p.Ala193Val (c.578C>T)?

DHH p.Ala193Val (c.578C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DHH p.Ala193Val (c.578C>T) in the general population?

DHH p.Ala193Val (c.578C>T) is very rare (popmax 0.0033%, sas) (gnomAD).

What do computational predictors say about DHH p.Ala193Val (c.578C>T)?

AlphaMissense predicts likely benign (score 0.276) — an in-silico prediction, not a clinical call.

DHH p.Ala193Val

c.578C>T · VCV4617293

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.276 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.276	likely benign
REVEL	0.834	moderately pathogenic-leaning
SaProt	LLR -10.42	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	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	27.0	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 0.0033% South Asian · 3/90,848 alleles

Filtering AF 0.000877% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000276% 4/1,449,662 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,283
European (non-Finnish)	8.48e-05%	1,179,782

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.Ala193Val
Coding: c.578C>T
MANE Select: NM_021044
Type: single nucleotide variant
Location: chr12:49090472 (GRCh38)
Gene constraint: LOEUF 0.999 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 5 PDB
Residue 193: a UniProt-annotated variant site (in gdmn; uncertain significance); a UniProt-annotated variant site (in gdmn); 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.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.Arg156Pro 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-ala193val (accessed [today's date]).

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