Is DHRS3 p.Ser175= (c.525C>T) pathogenic?

DHRS3 p.Ser175= (c.525C>T) is classified Likely benign in DHRS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). Ultra-rare (popmax 0.0574%, afr).

How common is DHRS3 p.Ser175= (c.525C>T) in the general population?

DHRS3 p.Ser175= (c.525C>T) is ultra-rare (popmax 0.0574%, afr) (gnomAD).

DHRS3 p.Ser175=

c.525C>T · rs145040210 · VCV2638255

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0574%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.4	GERP -4.7
Overall
CADD	5.059	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0574% African / African-American · 43/74,934 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.039%

Overall 0.00409% 66/1,613,764 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0574%	1,743
East Asian	0.00891%	11,225
Admixed American	0.00333%	29,996
Remaining individualsnot grpmax-eligible	0.0032%	31,240
South Asian	0.0022%	45,541
European (non-Finnish)	0.0011%	90,771

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.Ser175=
Coding: c.525C>T
MANE Select: NM_004753
dbSNP: rs145040210
Type: single nucleotide variant
Location: chr1:12578891 (GRCh38)
Gene constraint: LOEUF 0.79 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 94.16
Residue 175: a binding site

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-ser175 (accessed [today's date]).

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