Is CCSER2 p.Gln678Arg (c.2033A>G) pathogenic?

CCSER2 p.Gln678Arg (c.2033A>G) is classified Uncertain significance in CCSER2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-22). AlphaMissense: ambiguous (0.4821); Rare (popmax 0.172%, afr).

How common is CCSER2 p.Gln678Arg (c.2033A>G) in the general population?

CCSER2 p.Gln678Arg (c.2033A>G) is rare (popmax 0.172%, afr) (gnomAD).

What do computational predictors say about CCSER2 p.Gln678Arg (c.2033A>G)?

AlphaMissense predicts ambiguous (score 0.4821) — an in-silico prediction, not a clinical call.

CCSER2 p.Gln678Arg

c.2033A>G · rs61743630 · VCV2216468

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4821 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.172%, afr)

Computational evidence

Protein change
AlphaMissense	0.4821	ambiguous
REVEL	0.333	indeterminate
SaProt	LLR -9.34	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 143 kb · p 0.88 · regional, not allelic
Overall
CADD	27.4	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 0.172% African / African-American · 129/74,900 alleles

Filtering AF 0.148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.139%

Overall 0.0101% 163/1,610,018 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.172%	581
Middle Eastern	0.116%	863
Remaining individualsnot grpmax-eligible	0.0209%	4,793
Admixed American	0.0118%	8,462
South Asian	0.00443%	22,575
European (non-Finnish)	0.000255%	392,711

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.Gln678Arg
Coding: c.2033A>G
MANE Select: NM_001284240
dbSNP: rs61743630
Type: single nucleotide variant
Location: chr10:84438676 (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-gln678arg (accessed [today's date]).

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