Is PTCH2 p.Ser573Phe (c.1718C>T) pathogenic?

PTCH2 p.Ser573Phe (c.1718C>T) is classified Likely benign in PTCH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-26). AlphaMissense: likely benign (0.175); Rare (popmax 0.127%, sas); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Ser573Phe (c.1718C>T)?

PTCH2 p.Ser573Phe (c.1718C>T) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

How common is PTCH2 p.Ser573Phe (c.1718C>T) in the general population?

PTCH2 p.Ser573Phe (c.1718C>T) is rare (popmax 0.127%, sas) (gnomAD).

What do computational predictors say about PTCH2 p.Ser573Phe (c.1718C>T)?

AlphaMissense predicts likely benign (score 0.175) — an in-silico prediction, not a clinical call.

PTCH2 p.Ser573Phe

c.1718C>T · rs561039899 · VCV1105575

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.175 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.127%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nevoid basal cell carcinoma syndrome

Computational evidence

Protein change
AlphaMissense	0.175	likely benign
REVEL	0.785	moderately pathogenic-leaning
SaProt	LLR -10.15	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 21 kb · p 3.4e-06 · regional, not allelic
Overall
CADD	27.6	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 0.127% South Asian · 116/91,070 alleles

Filtering AF 0.108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.00756% 122/1,613,590 alleles · rare exomes 116/1,461,196 · genomes 6/152,394 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.127%	785
Remaining individualsnot grpmax-eligible	0.008%	12,501
European (non-Finnish)	8.47e-05%	1,180,011

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: PTCH2
Protein: p.Ser573Phe
Coding: c.1718C>T
MANE Select: NM_003738
dbSNP: rs561039899
Type: single nucleotide variant
Location: chr1:44828183 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25

Full PTCH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nevoid basal cell carcinoma syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTCH2 p.Ser573fs Uncertain significance ★ same residue
PTCH2 c.2976+2T>C Uncertain significance ★★ same condition
PTCH2 c.526-2A>G Uncertain significance ★★ same condition
PTCH2 c.618-6C>A Uncertain significance ★★ same condition
PTCH2 p.Ala1052Thr Uncertain significance ★★ ⚠ same condition
PTCH2 p.Ala1090Val Uncertain significance ★★ ⚠ same condition
PTCH2 p.Ala203Val Uncertain significance ★★ same condition
PTCH2 p.Ala21Thr 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/ptch2-p-ser573phe (accessed [today's date]).

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