Is DHRS3 p.Pro30Arg (c.89C>G) pathogenic?

DHRS3 p.Pro30Arg (c.89C>G) is classified Benign in DHRS3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-12). AlphaMissense: likely benign (0.2556); Low-frequency (popmax 1.05%, sas); Associated with DHRS3-related disorder.

What condition is associated with DHRS3 p.Pro30Arg (c.89C>G)?

DHRS3 p.Pro30Arg (c.89C>G) is associated with DHRS3-related disorder (ClinVar).

How common is DHRS3 p.Pro30Arg (c.89C>G) in the general population?

DHRS3 p.Pro30Arg (c.89C>G) is low-frequency (popmax 1.05%, sas) (gnomAD).

What do computational predictors say about DHRS3 p.Pro30Arg (c.89C>G)?

AlphaMissense predicts likely benign (score 0.2556) — an in-silico prediction, not a clinical call.

DHRS3 p.Pro30Arg

c.89C>G · rs201969624 · VCV3053427

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2556 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.05%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DHRS3-related disorder

Computational evidence

Protein change
AlphaMissense	0.2556	likely benign
REVEL	0.677	pathogenic-leaning
SaProt	LLR -10.72	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 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 49 kb · p 2.9e-05 · regional, not allelic
Overall
CADD	25.5	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 1.05% South Asian · 961/91,090 alleles

Filtering AF 1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.977%

Overall 0.0626% 1,011/1,613,820 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.05%	95
Remaining individualsnot grpmax-eligible	0.072%	1,389
Middle Eastern	0.0165%	6,060
Admixed American	0.00167%	60,032
African / African-American	0.00133%	75,058
European (non-Finnish)	0.000169%	589,995

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.Pro30Arg
Coding: c.89C>G
MANE Select: NM_004753
dbSNP: rs201969624
Type: single nucleotide variant
Location: chr1:12617260 (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

Disease context

DHRS3-related disorder

Similar variants

DHRS3 p.Gly150Ser Uncertain significance ★ ⚠ same condition
DHRS3 p.Val171Met Pathogenic same condition
DHRS3 p.Glu244Gln Uncertain significance ⚠ same condition
DHRS3 c.459+10A>C Benign same condition
DHRS3 p.Arg56Cys Likely benign ⚠ same condition
DHRS3 p.Thr80= Benign same condition
DHRS3 p.Ala125Gly Uncertain significance ★ ⚠ same type
DHRS3 p.Ala125Thr 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-pro30arg (accessed [today's date]).

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