Is DHRS3 p.Ala193Val (c.578C>T) pathogenic?

DHRS3 p.Ala193Val (c.578C>T) is classified Uncertain significance in DHRS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely pathogenic (0.6976); Very rare (popmax 0.00167%, amr).

How common is DHRS3 p.Ala193Val (c.578C>T) in the general population?

DHRS3 p.Ala193Val (c.578C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DHRS3 p.Ala193Val (c.578C>T)?

AlphaMissense predicts likely pathogenic (score 0.6976) — an in-silico prediction, not a clinical call.

DHRS3 p.Ala193Val

c.578C>T · VCV4011312

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6976 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6976	likely pathogenic
REVEL	0.757	pathogenic-leaning
SaProt	LLR -10.59	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 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 49 kb · p 2.9e-05 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,006 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000744% 12/1,613,888 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,006
African / African-American	0.00133%	74,926
European (non-Finnish)	0.000847%	118,003

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: DHRS3
Protein: p.Ala193Val
Coding: c.578C>T
MANE Select: NM_004753
Type: single nucleotide variant
Location: chr1:12578838 (GRCh38)
Gene constraint: LOEUF 0.79 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 94.16

Full DHRS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DHRS3 p.Ala125Gly Uncertain significance ★ ⚠ same type
DHRS3 p.Ala125Thr Uncertain significance ★ ⚠ same type
DHRS3 p.Ala214Thr Uncertain significance ★ ⚠ same type
DHRS3 p.Ala269Gly Uncertain significance ★ ⚠ same type
DHRS3 p.Ala269Val Uncertain significance ★ ⚠ same type
DHRS3 p.Ala280Thr Uncertain significance ★ ⚠ same type
DHRS3 p.Ala63Ser Uncertain significance ★ ⚠ same type
DHRS3 p.Arg100Gln Uncertain significance ★ ⚠ same type

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/dhrs3-p-ala193val (accessed [today's date]).

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