Is PPCS p.Phe56= (c.168C>T) pathogenic?

PPCS p.Phe56= (c.168C>T) is classified Likely benign in PPCS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). Very rare (popmax 0.00334%, amr).

How common is PPCS p.Phe56= (c.168C>T) in the general population?

PPCS p.Phe56= (c.168C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

PPCS p.Phe56=

c.168C>T · rs1207043808 · VCV2102205

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.38	GERP -4.3, phastCons 0.99
Overall
CADD	11.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,906 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,458,340 alleles · very rare

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: PPCS
Protein: p.Phe56=
Coding: c.168C>T
MANE Select: NM_024664
dbSNP: rs1207043808
Type: single nucleotide variant
Location: chr1:42456733 (GRCh38)
Gene constraint: LOEUF 1.064 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.94 · 2 PDB
Residue 56: a β-strand

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

Similar variants

PPCS p.Ala162Pro Uncertain significance ★★ ⚠ same type
PPCS p.Pro107Ser Uncertain significance ★★ ⚠ same type
PPCS c.*91T>G Benign ★★ same type
PPCS p.Leu280= Benign/Likely benign ★★ same type
PPCS p.Phe73= Likely benign ★★ same type
PPCS p.Ala8Ser Uncertain significance ★ ⚠ same type
PPCS p.Leu118Met Uncertain significance ★ ⚠ same type
PPCS p.Thr68Pro 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/ppcs-p-phe56 (accessed [today's date]).

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