Is HPSE p.Pro11Leu (c.32C>T) pathogenic?

HPSE p.Pro11Leu (c.32C>T) is classified Likely benign in HPSE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-27). AlphaMissense: likely benign (0.1068); No allele count reported in gnomAD v4.1 (AN 1,553,894).

How common is HPSE p.Pro11Leu (c.32C>T) in the general population?

HPSE p.Pro11Leu (c.32C>T) is no allele count reported in gnomAD v4.1 (AN 1,553,894) (gnomAD).

What do computational predictors say about HPSE p.Pro11Leu (c.32C>T)?

AlphaMissense predicts likely benign (score 0.1068) — an in-silico prediction, not a clinical call.

HPSE p.Pro11Leu

c.32C>T · rs1657125906 · VCV2489131

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1068 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,553,894)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1068	likely benign
REVEL	0.003	strongly benign-leaning
SaProt	LLR -3.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -1.6
Regional constraint	o/e 1.01	unconstrained · MANE · 39 kb · p 0.8 · regional, not allelic
Overall
CADD	2.827	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,553,894). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: HPSE
Protein: p.Pro11Leu
Coding: c.32C>T
MANE Select: NM_001098540
dbSNP: rs1657125906
Type: single nucleotide variant
Location: chr4:83334751 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.02 · 58 PDB

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

Similar variants

HPSE c.673+8C>A Benign ★★ same type
HPSE p.Gly370Asp Likely benign ★★ same type
HPSE p.Ala177Gly Uncertain significance ★ ⚠ same type
HPSE p.Ala204Thr Uncertain significance ★ ⚠ same type
HPSE p.Ala285Thr Uncertain significance ★ ⚠ same type
HPSE p.Ala305Thr Uncertain significance ★ ⚠ same type
HPSE p.Ala84Thr Uncertain significance ★ ⚠ same type
HPSE p.Arg303Trp 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/hpse-p-pro11leu (accessed [today's date]).

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