Is CCPG1 p.Leu278Ser (c.833T>C) pathogenic?

CCPG1 p.Leu278Ser (c.833T>C) is classified Uncertain significance in CCPG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-18). AlphaMissense: likely benign (0.2749); Very rare (popmax 0.00684%, eas).

How common is CCPG1 p.Leu278Ser (c.833T>C) in the general population?

CCPG1 p.Leu278Ser (c.833T>C) is very rare (popmax 0.00684%, eas) (gnomAD).

What do computational predictors say about CCPG1 p.Leu278Ser (c.833T>C)?

AlphaMissense predicts likely benign (score 0.2749) — an in-silico prediction, not a clinical call.

CCPG1 p.Leu278Ser

c.833T>C · rs201264073 · VCV2548961

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2749 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00684%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2749	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -10.34	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 3, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 26 kb · p 0.52 · regional, not allelic
Overall
CADD	20.2	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 0.00684% East Asian · 3/43,862 alleles

Filtering AF 0.00181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000903%

Overall 0.000393% 6/1,528,632 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00684%	14,621
European (non-Finnish)	0.000262%	381,002

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: CCPG1
Protein: p.Leu278Ser
Coding: c.833T>C
MANE Select: NM_001204450
dbSNP: rs201264073
Type: single nucleotide variant
Location: chr15:55360940 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.96 · 1 PDB
Residue 278: the 'interaction with mcf2l and src' region

Full CCPG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PIGB p.Ile537Met Pathogenic/Likely pathogenic ★★ ⚠ same type
PIGB p.Lys551Thr Benign ★★ same type
PIGB p.Ser509= Benign ★★ same type
CCPG1 p.Ala576Val Uncertain significance ★ ⚠ same type
CCPG1 p.Ala75Thr Uncertain significance ★ ⚠ same type
CCPG1 p.Arg179His Uncertain significance ★ ⚠ same type
CCPG1 p.Arg193Gln Uncertain significance ★ ⚠ same type
CCPG1 p.Arg193Trp 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/ccpg1-p-leu278ser (accessed [today's date]).

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