Is CCSER2 p.Pro207Gln (c.620C>A) pathogenic?

CCSER2 p.Pro207Gln (c.620C>A) is classified Uncertain significance in CCSER2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-04). AlphaMissense: likely benign (0.1247); Very rare (popmax 0.0078%, nfe).

How common is CCSER2 p.Pro207Gln (c.620C>A) in the general population?

CCSER2 p.Pro207Gln (c.620C>A) is very rare (popmax 0.0078%, nfe) (gnomAD).

What do computational predictors say about CCSER2 p.Pro207Gln (c.620C>A)?

AlphaMissense predicts likely benign (score 0.1247) — an in-silico prediction, not a clinical call.

CCSER2 p.Pro207Gln

c.620C>A · rs375626713 · VCV3140154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1247 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0078%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1247	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -6.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.18, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 143 kb · p 0.88 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0078% European (non-Finnish) · 92/1,179,890 alleles

Filtering AF 0.00648% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.006%

Overall 0.00595% 96/1,613,670 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0078%	12,825
Remaining individualsnot grpmax-eligible	0.0048%	20,827
Finnishnot grpmax-eligible	0.00156%	63,900

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.Pro207Gln
Coding: c.620C>A
MANE Select: NM_001284240
dbSNP: rs375626713
Type: single nucleotide variant
Location: chr10:84371672 (GRCh38)
Gene constraint: LOEUF 0.589 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 48.62
Residue 207: the 'disordered' region

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-pro207gln (accessed [today's date]).

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