Is PTCHD1 p.Pro32Arg (c.95C>G) pathogenic?

PTCHD1 p.Pro32Arg (c.95C>G) is classified Likely pathogenic in PTCHD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-27). AlphaMissense: likely pathogenic (0.9979); Very rare (popmax 0.000112%, nfe); Associated with intellectual disability.

What condition is associated with PTCHD1 p.Pro32Arg (c.95C>G)?

PTCHD1 p.Pro32Arg (c.95C>G) is associated with intellectual disability (ClinVar).

How common is PTCHD1 p.Pro32Arg (c.95C>G) in the general population?

PTCHD1 p.Pro32Arg (c.95C>G) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about PTCHD1 p.Pro32Arg (c.95C>G)?

AlphaMissense predicts likely pathogenic (score 0.9979) — an in-silico prediction, not a clinical call.

PTCHD1 p.Pro32Arg

c.95C>G · rs1569130365 · VCV1064443

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9979 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.9979	likely pathogenic ✓ concordant with ClinVar · top 1% in PTCHD1
REVEL	0.901	moderately pathogenic-leaning
SaProt	LLR -19.67	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 59 kb · p 4.1e-12 · regional, not allelic
Overall
CADD	33.0	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 0.000112% European (non-Finnish) · 1/894,538 alleles

Overall 8.27e-05% 1/1,209,826 alleles · very rare exomes 1/1,096,460 · genomes 0/113,366 · 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: PTCHD1
Protein: p.Pro32Arg
Coding: c.95C>G
MANE Select: NM_173495
dbSNP: rs1569130365
Type: single nucleotide variant
Location: chrX:23334970 (GRCh38)
Structure: AlphaFold pLDDT 84.14
Residue 32: a UniProt-annotated variant site (found in a patient with a neurodevelopmental disorder; uncertain significance; decreased localization to cell membrane); a UniProt-annotated variant site (likely risk factor for autsx4; decreased localization to cell membrane; the orthologous mouse mutation results in defective post-translational processing and glycosylation; decreased protein half-life and stability)

Full PTCHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTCHD1 p.Pro32Leu Uncertain significance ★ ⚠ same residue
PTCHD1 p.Tyr213Cys Conflicting classifications of pathogenicity ⚠ same condition
PTCHD1 p.Ala314Thr Uncertain significance ★★ ⚠ same type
PTCHD1 p.Arg238Ser Uncertain significance ★★ ⚠ same type
PTCHD1 p.Arg266= Uncertain significance ★★ same type
PTCHD1 p.Arg294His Uncertain significance ★★ ⚠ same type
PTCHD1 p.Arg596Trp Uncertain significance ★★ ⚠ same type
PTCHD1 p.Asn818Ser 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/ptchd1-p-pro32arg (accessed [today's date]).

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