Is PTCH1 p.Ser554= (c.1662C>T) pathogenic?

PTCH1 p.Ser554= (c.1662C>T) is classified Likely benign in PTCH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-24). Very rare (popmax 0.00333%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with PTCH1 p.Ser554= (c.1662C>T)?

PTCH1 p.Ser554= (c.1662C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PTCH1 p.Ser554= (c.1662C>T) in the general population?

PTCH1 p.Ser554= (c.1662C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

PTCH1 p.Ser554=

c.1662C>T · rs769847137 · VCV2564350

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Overall
CADD	14.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,012 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000186% 3/1,613,844 alleles · very rare exomes 3/1,461,536 · genomes 0/152,308 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,006
South Asian	0.0011%	90,996

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: PTCH1
Protein: p.Ser554=
Coding: c.1662C>T
MANE Select: NM_000264
dbSNP: rs769847137
Type: single nucleotide variant
Location: chr9:95476100 (GRCh38)
Gene constraint: LOEUF 0.146 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 74.36 · 16 PDB
Residue 554: the ssd domain

Full PTCH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTCH1 p.Ser554Asn Likely benign ★★ same residue
PTCH1 p.Ser554Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
PTCH1 p.Ser554Arg Likely pathogenic ★★ same residue
PTCH1 p.Ser554Thr Uncertain significance ★ ⚠ same residue
PTCH1 c.1068-1G>T Likely pathogenic ★★ same condition
PTCH1 c.1216-1G>A Pathogenic/Likely pathogenic ★★ same condition
PTCH1 c.1347+1G>C Likely pathogenic ★★ same condition
PTCH1 c.202-2A>C Pathogenic/Likely pathogenic ★★ 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/ptch1-p-ser554 (accessed [today's date]).

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