Is DHRS3 p.Ile170Val (c.508A>G) pathogenic?

DHRS3 p.Ile170Val (c.508A>G) is classified Uncertain significance in DHRS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely benign (0.1266); Very rare (popmax 0.00223%, eas).

How common is DHRS3 p.Ile170Val (c.508A>G) in the general population?

DHRS3 p.Ile170Val (c.508A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DHRS3 p.Ile170Val (c.508A>G)?

AlphaMissense predicts likely benign (score 0.1266) — an in-silico prediction, not a clinical call.

DHRS3 p.Ile170Val

c.508A>G · VCV4659901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1266 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1266	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -7.84	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 49 kb · p 2.9e-05 · regional, not allelic
Overall
CADD	21.2	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 0.00223% East Asian · 1/44,890 alleles

Overall 0.000124% 2/1,613,594 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,890
European (non-Finnish)	8.47e-05%	1,180,012

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.Ile170Val
Coding: c.508A>G
MANE Select: NM_004753
Type: single nucleotide variant
Location: chr1:12578908 (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-ile170val (accessed [today's date]).

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