Is CPZ p.Ser77= (c.231C>T) pathogenic?

CPZ p.Ser77= (c.231C>T) is classified Benign in CPZ (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-26). Rare (popmax 0.504%, eas); Associated with CPZ-related disorder.

What condition is associated with CPZ p.Ser77= (c.231C>T)?

CPZ p.Ser77= (c.231C>T) is associated with CPZ-related disorder (ClinVar).

How common is CPZ p.Ser77= (c.231C>T) in the general population?

CPZ p.Ser77= (c.231C>T) is rare (popmax 0.504%, eas) (gnomAD).

CPZ p.Ser77=

c.231C>T · rs150089485 · VCV3044860

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.504%, eas)

Conditions

CPZ-related disorder

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 -12	GERP -1.9
Overall
CADD	8.462	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.504% East Asian · 226/44,838 alleles

Filtering AF 0.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.429%

Overall 0.355% 5,731/1,613,424 alleles · rare exomes 5,385/1,461,178 · genomes 346/152,246 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.504%	198
Remaining individualsnot grpmax-eligible	0.462%	216
European (non-Finnish)	0.428%	233
African / African-American	0.0986%	1,014
Admixed American	0.0733%	1,364
Finnishnot grpmax-eligible	0.0409%	2,443
Ashkenazi Jewishnot grpmax-eligible	0.0406%	2,466
Middle Eastern	0.033%	3,031
South Asian	0.00329%	30,353

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: CPZ
Protein: p.Ser77=
Coding: c.231C>T
MANE Select: NM_001014447
dbSNP: rs150089485
Type: single nucleotide variant
Location: chr4:8601232 (GRCh38)
Gene constraint: LOEUF 1.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.33
Residue 77: the fz domain

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

Disease context

CPZ-related disorder

Similar variants

CPZ p.Ser77Phe Uncertain significance ★ ⚠ same residue
CPZ p.Ala205Thr Uncertain significance ⚠ same condition
CPZ p.Gly575Arg Uncertain significance same condition
CPZ c.1363+6G>T Benign same condition
CPZ c.1504-3C>T Benign same condition
CPZ c.497-5C>G Likely benign same condition
CPZ c.-10C>T Likely benign same condition
CPZ c.*4C>T Benign 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/cpz-p-ser77 (accessed [today's date]).

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