Is HPD p.Arg55Trp (c.163C>T) pathogenic?

HPD p.Arg55Trp (c.163C>T) is classified Uncertain significance in HPD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-03). AlphaMissense: ambiguous (0.3913); Very rare (popmax 0.000254%, nfe).

How common is HPD p.Arg55Trp (c.163C>T) in the general population?

HPD p.Arg55Trp (c.163C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about HPD p.Arg55Trp (c.163C>T)?

AlphaMissense predicts ambiguous (score 0.3913) — an in-silico prediction, not a clinical call.

HPD p.Arg55Trp

c.163C>T · rs2137633084 · VCV1696213

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3913 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.3913	ambiguous
REVEL	0.71	pathogenic-leaning
SaProt	LLR -11.47	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2	GERP 0.92, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 19 kb · p 0.004 · regional, not allelic
Overall
CADD	24.5	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 0.000254% European (non-Finnish) · 3/1,179,894 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,996 alleles · very rare exomes 3/1,461,738 · genomes 0/152,258 · joint denominator

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.Arg55Trp
Coding: c.163C>T
MANE Select: NM_002150
dbSNP: rs2137633084
Type: single nucleotide variant
Location: chr12:121857363 (GRCh38)

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

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-arg55trp (accessed [today's date]).

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