Is HPD p.Ala97Val (c.290C>T) pathogenic?

HPD p.Ala97Val (c.290C>T) is classified Uncertain significance in HPD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-25). AlphaMissense: ambiguous (0.5466); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with HPD p.Ala97Val (c.290C>T)?

HPD p.Ala97Val (c.290C>T) is associated with Inborn genetic diseases (ClinVar).

How common is HPD p.Ala97Val (c.290C>T) in the general population?

HPD p.Ala97Val (c.290C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about HPD p.Ala97Val (c.290C>T)?

AlphaMissense predicts ambiguous (score 0.5466) — an in-silico prediction, not a clinical call.

HPD p.Ala97Val

c.290C>T · rs984792300 · VCV2279873

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5466 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5466	ambiguous
REVEL	0.693	pathogenic-leaning
SaProt	LLR -12.17	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 19 kb · p 0.004 · regional, not allelic
Overall
CADD	23.5	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

Grpmax group 0.0011% South Asian · 1/91,072 alleles

Overall 0.000137% 2/1,461,792 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,072
European (non-Finnish)	8.47e-05%	1,179,948

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: HPD
Protein: p.Ala97Val
Coding: c.290C>T
MANE Select: NM_002150
dbSNP: rs984792300
Type: single nucleotide variant
Location: chr12:121856358 (GRCh38)
Gene constraint: LOEUF 0.845 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.00 · 4 PDB
Residue 97: the voc 1 domain; a β-strand

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.Ala97= 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 p.Asp167Asn Benign/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/hpd-p-ala97val (accessed [today's date]).

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