Is DHRS3 p.Arg61Pro (c.182G>C) pathogenic?

DHRS3 p.Arg61Pro (c.182G>C) is classified Uncertain significance in DHRS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely pathogenic (0.9019); Absent from gnomAD v4.1.

How common is DHRS3 p.Arg61Pro (c.182G>C) in the general population?

DHRS3 p.Arg61Pro (c.182G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHRS3 p.Arg61Pro (c.182G>C)?

AlphaMissense predicts likely pathogenic (score 0.9019) — an in-silico prediction, not a clinical call.

DHRS3 p.Arg61Pro

c.182G>C · VCV4240073

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9019 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9019	likely pathogenic
REVEL	0.767	pathogenic-leaning
SaProt	LLR -14.73	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 5.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 49 kb · p 2.9e-05 · regional, not allelic
Overall
CADD	24.6	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

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: DHRS3
Protein: p.Arg61Pro
Coding: c.182G>C
MANE Select: NM_004753
Type: single nucleotide variant
Location: chr1:12617167 (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.Ala193Val 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

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-arg61pro (accessed [today's date]).

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