Is DHRS2 p.Arg7Trp (c.19C>T) pathogenic?

DHRS2 p.Arg7Trp (c.19C>T) is classified Likely benign in DHRS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-09). AlphaMissense: likely benign (0.1541); Rare (popmax 0.164%, afr).

How common is DHRS2 p.Arg7Trp (c.19C>T) in the general population?

DHRS2 p.Arg7Trp (c.19C>T) is rare (popmax 0.164%, afr) (gnomAD).

What do computational predictors say about DHRS2 p.Arg7Trp (c.19C>T)?

AlphaMissense predicts likely benign (score 0.1541) — an in-silico prediction, not a clinical call.

DHRS2 p.Arg7Trp

c.19C>T · rs150047105 · VCV765120

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1541 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.164%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1541	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -9.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.3	GERP -3.9
Regional constraint	o/e 1.20	unconstrained · MANE · 6,385 bp · p 0.00018 · regional, not allelic
Overall
CADD	9.781	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 0.164% African / African-American · 123/75,044 alleles

Filtering AF 0.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.131%

Overall 0.0112% 181/1,613,966 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.164%	610
Admixed American	0.00833%	12,000
Remaining individualsnot grpmax-eligible	0.0064%	15,624
European (non-Finnish)	0.00381%	26,221
South Asian	0.0033%	30,347
East Asian	0.00223%	44,866

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: DHRS2
Protein: p.Arg7Trp
Coding: c.19C>T
MANE Select: NM_005794
dbSNP: rs150047105
Type: single nucleotide variant
Location: chr14:23638883 (GRCh38)
Gene constraint: LOEUF 1.4 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.37

Full DHRS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DHRS2 p.Arg279= Benign/Likely benign ★★ same type
DHRS2 p.Cys92= Benign ★★ same type
DHRS2 p.Gly84Arg Likely benign ★★ ⚠ same type
DHRS2 c.*2A>T Uncertain significance ★ same type
DHRS2 c.*3G>A Uncertain significance ★ same type
DHRS2 c.*42G>A Uncertain significance ★ same type
DHRS2 p.Ala17Gly Uncertain significance ★ ⚠ same type
DHRS2 p.Ala263Thr 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/dhrs2-p-arg7trp (accessed [today's date]).

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