Is HMGCS2 p.Pro201= (c.603C>T) pathogenic?

HMGCS2 p.Pro201= (c.603C>T) is classified Likely benign in HMGCS2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-25). Absent from gnomAD v4.1; Associated with HMGCS2-related disorder.

What condition is associated with HMGCS2 p.Pro201= (c.603C>T)?

HMGCS2 p.Pro201= (c.603C>T) is associated with HMGCS2-related disorder (ClinVar).

How common is HMGCS2 p.Pro201= (c.603C>T) in the general population?

HMGCS2 p.Pro201= (c.603C>T) is absent from gnomAD v4.1 (gnomAD).

HMGCS2 p.Pro201=

c.603C>T · rs2464266480 · VCV3058296

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

HMGCS2-related disorder

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 0.8	GERP -3.6, phastCons 0.3
Overall
CADD	6.748	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: HMGCS2
Protein: p.Pro201=
Coding: c.603C>T
MANE Select: NM_005518
dbSNP: rs2464266480
Type: single nucleotide variant
Location: chr1:119759946 (GRCh38)
Gene constraint: LOEUF 1.111 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.00 · 1 PDB

Full HMGCS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

HMGCS2-related disorder

Similar variants

HMGCS2 p.Pro201Arg Uncertain significance ★ ⚠ same residue
HMGCS2 c.1016+1G>A Pathogenic ★★ same condition
HMGCS2 p.Arg424Ter Pathogenic/Likely pathogenic ★★ same condition
HMGCS2 p.Asn318Ser Uncertain significance ★★ ⚠ same condition
HMGCS2 p.Gly210Glu Uncertain significance ⚠ same condition
HMGCS2 p.Asp496= Likely benign same condition
HMGCS2 p.Glu132= Likely benign same condition
HMGCS2 p.Pro51= Likely benign 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/hmgcs2-p-pro201 (accessed [today's date]).

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