Is DHCR7 p.Arg362= (c.1086C>T) pathogenic?

DHCR7 p.Arg362= (c.1086C>T) is classified Likely benign in DHCR7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-13). Very rare (popmax 0.00666%, amr); Associated with Smith-Lemli-Opitz syndrome.

What condition is associated with DHCR7 p.Arg362= (c.1086C>T)?

DHCR7 p.Arg362= (c.1086C>T) is associated with Smith-Lemli-Opitz syndrome (ClinVar).

How common is DHCR7 p.Arg362= (c.1086C>T) in the general population?

DHCR7 p.Arg362= (c.1086C>T) is very rare (popmax 0.00666%, amr) (gnomAD).

DHCR7 p.Arg362=

c.1086C>T · rs1459497627 · VCV1107265

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Conditions

Smith-Lemli-Opitz syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.311	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.24	GERP -3.2, phastCons 0.065
Overall
CADD	5.982	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00666% Admixed American · 4/60,026 alleles

Filtering AF 0.00225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000411% 6/1,460,700 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00666%	15,006
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	8.48e-05%	1,179,844

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: DHCR7
Protein: p.Arg362=
Coding: c.1086C>T
MANE Select: NM_001360
dbSNP: rs1459497627
Type: single nucleotide variant
Location: chr11:71435717 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.64
Residue 362: a binding site; a UniProt-annotated variant site (in slos)

Full DHCR7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Smith-Lemli-Opitz syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHCR7 p.Arg362Gly Likely pathogenic ★ same residue
DHCR7 p.Arg362Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
DHCR7 p.Arg362His Conflicting classifications of pathogenicity ★ ⚠ same residue
DHCR7 p.Arg362fs Likely pathogenic ★ same residue
DHCR7 c.322-1G>A Likely pathogenic ★★ same condition
DHCR7 c.412+3A>T Likely pathogenic ★★ same condition
DHCR7 c.413-2A>G Likely pathogenic ★★ same condition
DHCR7 c.626+1G>A Likely pathogenic ★★ same condition

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/dhcr7-p-arg362 (accessed [today's date]).

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