Is PTCHD1 p.Ser371Phe (c.1112C>T) pathogenic?

PTCHD1 p.Ser371Phe (c.1112C>T) is classified Uncertain significance in PTCHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-03). AlphaMissense: likely pathogenic (0.8297); Very rare (popmax 0.00352%, sas).

How common is PTCHD1 p.Ser371Phe (c.1112C>T) in the general population?

PTCHD1 p.Ser371Phe (c.1112C>T) is very rare (popmax 0.00352%, sas) (gnomAD).

What do computational predictors say about PTCHD1 p.Ser371Phe (c.1112C>T)?

AlphaMissense predicts likely pathogenic (score 0.8297) — an in-silico prediction, not a clinical call.

PTCHD1 p.Ser371Phe

c.1112C>T · VCV4949363

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8297 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00352%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8297	likely pathogenic
REVEL	0.587	indeterminate
SaProt	LLR -9.74	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 59 kb · p 4.1e-12 · regional, not allelic
Overall
CADD	25.9	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 0.00352% South Asian · 2/56,816 alleles

Filtering AF 0.000584% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000219%

Overall 0.000166% 2/1,205,630 alleles · very rare exomes 2/1,091,712 · genomes 0/113,918 · 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.Ser371Phe
Coding: c.1112C>T
MANE Select: NM_173495
Type: single nucleotide variant
Location: chrX:23392630 (GRCh38)
Structure: AlphaFold pLDDT 84.14
Residue 371: the ssd domain

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

Similar variants

PTCHD1 p.Pro32Arg Likely pathogenic ★★ same type
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
PTCHD1 p.Asp663His 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-ser371phe (accessed [today's date]).

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