Is HPGD p.Ser137= (c.411A>G) pathogenic?

HPGD p.Ser137= (c.411A>G) is classified Likely benign in HPGD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). Absent from gnomAD v4.1.

How common is HPGD p.Ser137= (c.411A>G) in the general population?

HPGD p.Ser137= (c.411A>G) is absent from gnomAD v4.1 (gnomAD).

HPGD p.Ser137=

c.411A>G · VCV4773153

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.64	GERP -3.7, phastCons 0.007
Overall
CADD	7.137	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: HPGD
Protein: p.Ser137=
Coding: c.411A>G
MANE Select: NM_000860
Type: single nucleotide variant
Location: chr4:174508706 (GRCh38)
Gene constraint: LOEUF 1.28 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.82 · 6 PDB

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

Similar variants

HPGD c.218-1G>A Pathogenic ★★ same type
HPGD c.324+5G>A Pathogenic ★★ same type
HPGD c.421+1G>T Pathogenic ★★ same type
HPGD p.Ala140Pro Pathogenic ★★ same type
HPGD p.Gln68Ter Pathogenic ★★ same type
HPGD c.*157A>G Uncertain significance ★★ same type
HPGD p.Asn95Ser Uncertain significance ★★ ⚠ same type
HPGD p.Glu195Ala 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/hpgd-p-ser137 (accessed [today's date]).

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