Is KDSR p.Val87= (c.261G>A) pathogenic?

KDSR p.Val87= (c.261G>A) is classified Benign in KDSR (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 67.4%, sas) — too common for a highly-penetrant pathogenic allele; Associated with erythrokeratodermia variabilis et progressiva 4.

What condition is associated with KDSR p.Val87= (c.261G>A)?

KDSR p.Val87= (c.261G>A) is associated with erythrokeratodermia variabilis et progressiva 4 (ClinVar).

How is Erythrokeratodermia variabilis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

KDSR p.Val87=

Q: How common is KDSR p.Val87= (c.261G>A) in the general population?

KDSR p.Val87= (c.261G>A) is common (popmax 67.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.261G>A · rs2003149 · VCV1300062

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 67.4%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

erythrokeratodermia variabilis et progressiva 4

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 -0.33	GERP -5, phastCons 0.088
Overall
CADD	7.571	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 67.4% South Asian · 57,485/85,254 alleles

Filtering AF 67% ClinGen BA1/BS1 input FAF95, joint · FAF99 66.8%

Overall 64.4% 1,019,591/1,583,240 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	67.4%	1
Amishnot grpmax-eligible	66.6%	2
European (non-Finnish)	66%	2
Finnishnot grpmax-eligible	65.8%	2
Remaining individualsnot grpmax-eligible	62.9%	2
Admixed American	62.4%	2
Ashkenazi Jewishnot grpmax-eligible	60.9%	2
Middle Eastern	60.8%	2
African / African-American	48.7%	2
East Asian	48.1%	2

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: KDSR
Protein: p.Val87=
Coding: c.261G>A
MANE Select: NM_002035
dbSNP: rs2003149
Type: single nucleotide variant
Location: chr18:63355558 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 95.40
Residue 87: a UniProt-annotated variant site (in ekvp4; loss of 3-dehydrosphinganine reductase activity)

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

Disease context

erythrokeratodermia variabilis et progressiva 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Erythrokeratodermia variabilis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

KDSR p.Gln293= Likely pathogenic ★★ same condition
KDSR p.Arg64Ter Likely pathogenic ★ same condition
KDSR p.Gly182Ser Likely pathogenic ★ same condition
KDSR c.256-2A>C Pathogenic same condition
KDSR p.Tyr186Phe Pathogenic same condition
KDSR p.Gln55_Gly56delinsArg Pathogenic same condition
KDSR p.Arg317His Uncertain significance ★★ ⚠ same type
KDSR p.Gly56Val 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/kdsr-p-val87 (accessed [today's date]).

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