Is DHCR24 p.Arg330Cys (c.988C>T) pathogenic?

DHCR24 p.Arg330Cys (c.988C>T) is classified Uncertain significance in DHCR24 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-06). AlphaMissense: likely pathogenic (0.9638); Very rare (popmax 0.00439%, sas); Associated with Inborn genetic diseases.

What condition is associated with DHCR24 p.Arg330Cys (c.988C>T)?

DHCR24 p.Arg330Cys (c.988C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DHCR24 p.Arg330Cys (c.988C>T) in the general population?

DHCR24 p.Arg330Cys (c.988C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about DHCR24 p.Arg330Cys (c.988C>T)?

AlphaMissense predicts likely pathogenic (score 0.9638) — an in-silico prediction, not a clinical call.

DHCR24 p.Arg330Cys

c.988C>T · rs754424849 · VCV1046275

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9638 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9638	likely pathogenic
REVEL	0.877	moderately pathogenic-leaning
SaProt	LLR -13.33	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 35 kb · p 6.2e-08 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00439% South Asian · 4/91,078 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000372% 6/1,613,684 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,769
African / African-American	0.00133%	74,922
European (non-Finnish)	8.48e-05%	1,179,856

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: DHCR24
Protein: p.Arg330Cys
Coding: c.988C>T
MANE Select: NM_014762
dbSNP: rs754424849
Type: single nucleotide variant
Location: chr1:54865335 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 92.40

Full DHCR24 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHCR24 p.Arg132His Uncertain significance ★★ ⚠ same condition
DHCR24 p.Arg230Cys Uncertain significance ★★ ⚠ same condition
DHCR24 p.Arg230His Uncertain significance ★★ ⚠ same condition
DHCR24 p.Arg241His Uncertain significance ★★ ⚠ same condition
DHCR24 p.Arg261Trp Uncertain significance ★★ ⚠ same condition
DHCR24 p.Gln84Glu Uncertain significance ★★ ⚠ same condition
DHCR24 p.Ile251Val Uncertain significance ★★ ⚠ same condition
DHCR24 p.Leu271Ile Uncertain significance ★★ ⚠ 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/dhcr24-p-arg330cys (accessed [today's date]).

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