Is CCSER2 p.Pro561Ser (c.1681C>T) pathogenic?

CCSER2 p.Pro561Ser (c.1681C>T) is classified Uncertain significance in CCSER2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-13). AlphaMissense: ambiguous (0.4666); Very rare (popmax 0.00167%, amr).

How common is CCSER2 p.Pro561Ser (c.1681C>T) in the general population?

CCSER2 p.Pro561Ser (c.1681C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CCSER2 p.Pro561Ser (c.1681C>T)?

AlphaMissense predicts ambiguous (score 0.4666) — an in-silico prediction, not a clinical call.

CCSER2 p.Pro561Ser

c.1681C>T · rs1259377452 · VCV3140146

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4666 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
AlphaMissense	0.4666	ambiguous
REVEL	0.352	indeterminate
SaProt	LLR -5.61	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 143 kb · p 0.88 · regional, not allelic
Overall
CADD	27.6	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 0.00167% Admixed American · 1/59,956 alleles

Overall 0.000658% 1/152,042 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: CCSER2
Protein: p.Pro561Ser
Coding: c.1681C>T
MANE Select: NM_001284240
dbSNP: rs1259377452
Type: single nucleotide variant
Location: chr10:84417837 (GRCh38)
Gene constraint: LOEUF 0.589 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 48.62

Full CCSER2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCSER2 c.2326-13498G>A Uncertain significance ★ ⚠ same type
CCSER2 c.2326-13517C>T Uncertain significance ★ ⚠ same type
CCSER2 c.2326-13535T>G Uncertain significance ★ ⚠ same type
CCSER2 c.2326-13543G>T Uncertain significance ★ ⚠ same type
CCSER2 c.2326-13552T>C Uncertain significance ★ ⚠ same type
CCSER2 c.2326-13556T>C Uncertain significance ★ ⚠ same type
CCSER2 c.2326-13558C>T Uncertain significance ★ ⚠ same type
CCSER2 p.Ala125Gly 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/ccser2-p-pro561ser (accessed [today's date]).

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