Is PTCH2 p.Ala511= (c.1533C>T) pathogenic?

PTCH2 p.Ala511= (c.1533C>T) is classified Benign in PTCH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-31). Rare (popmax 0.247%, eas); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Ala511= (c.1533C>T)?

PTCH2 p.Ala511= (c.1533C>T) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

How common is PTCH2 p.Ala511= (c.1533C>T) in the general population?

PTCH2 p.Ala511= (c.1533C>T) is rare (popmax 0.247%, eas) (gnomAD).

PTCH2 p.Ala511=

c.1533C>T · rs76854674 · VCV415449

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.247%, eas)

Conditions

nevoid basal cell carcinoma 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 -7.7	GERP -4.1
Overall
CADD	1.258	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.247% East Asian · 111/44,878 alleles

Filtering AF 0.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.196%

Overall 0.0125% 201/1,614,070 alleles · rare exomes 179/1,461,730 · genomes 22/152,340 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.247%	404
Remaining individualsnot grpmax-eligible	0.0144%	6,944
South Asian	0.00878%	11,384
African / African-American	0.00666%	15,011
European (non-Finnish)	0.00551%	18,154
Admixed American	0.00333%	30,002
Finnishnot grpmax-eligible	0.00156%	64,012

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.Ala511=
Coding: c.1533C>T
MANE Select: NM_003738
dbSNP: rs76854674
Type: single nucleotide variant
Location: chr1:44828563 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25
Residue 511: the ssd domain

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.Ala511Thr 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-ala511 (accessed [today's date]).

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