Is DHRS2 p.Ile52Val (c.154A>G) pathogenic?

DHRS2 p.Ile52Val (c.154A>G) is classified Uncertain significance in DHRS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.0873); Ultra-rare (popmax 0.0343%, mid).

How common is DHRS2 p.Ile52Val (c.154A>G) in the general population?

DHRS2 p.Ile52Val (c.154A>G) is ultra-rare (popmax 0.0343%, mid) (gnomAD).

What do computational predictors say about DHRS2 p.Ile52Val (c.154A>G)?

AlphaMissense predicts likely benign (score 0.0873) — an in-silico prediction, not a clinical call.

DHRS2 p.Ile52Val

c.154A>G · rs1216706022 · VCV2312031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0873 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0343%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0873	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -8.85	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 0.031	GERP -0.15
Regional constraint	o/e 1.20	unconstrained · MANE · 6,385 bp · p 0.00018 · regional, not allelic
Overall
CADD	1.478	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0343% Middle Eastern · 2/5,836 alleles

Filtering AF 0.00603% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0025%

Overall 0.000205% 3/1,461,186 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0343%	2,918
South Asian	0.0011%	90,984

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.Ile52Val
Coding: c.154A>G
MANE Select: NM_005794
dbSNP: rs1216706022
Type: single nucleotide variant
Location: chr14:23639192 (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.Arg7Trp 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

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-ile52val (accessed [today's date]).

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