Is HPD p.Asp167Val (c.500A>T) pathogenic?

HPD p.Asp167Val (c.500A>T) is classified Uncertain significance in HPD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: ambiguous (0.445); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with HPD p.Asp167Val (c.500A>T)?

HPD p.Asp167Val (c.500A>T) is associated with Inborn genetic diseases (ClinVar).

How common is HPD p.Asp167Val (c.500A>T) in the general population?

HPD p.Asp167Val (c.500A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HPD p.Asp167Val (c.500A>T)?

AlphaMissense predicts ambiguous (score 0.445) — an in-silico prediction, not a clinical call.

HPD p.Asp167Val

c.500A>T · VCV4036119

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.445 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.445	ambiguous
REVEL	0.454	indeterminate
SaProt	LLR -14.98	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 19 kb · p 0.004 · regional, not allelic
Overall
CADD	23.2	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

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: HPD
Protein: p.Asp167Val
Coding: c.500A>T
MANE Select: NM_002150
Type: single nucleotide variant
Location: chr12:121849705 (GRCh38)
Gene constraint: LOEUF 0.845 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.00 · 4 PDB

Full HPD 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

HPD p.Asp167Asn Benign/Likely benign ★★ ⚠ same residue
HPD c.198+3G>A Uncertain significance ★★ same condition
HPD p.Arg279Cys Uncertain significance ★★ ⚠ same condition
HPD p.Arg300Trp Uncertain significance ★★ ⚠ same condition
HPD p.Asp182Glu Uncertain significance ★★ ⚠ same condition
HPD p.Gly159Glu Uncertain significance ★★ ⚠ same condition
HPD p.Thr2Met Uncertain significance ★★ ⚠ same condition
HPD c.3+4A>C 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/hpd-p-asp167val (accessed [today's date]).

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