Is CCSER2 p.Asp559Glu (c.1677T>A) pathogenic?

CCSER2 p.Asp559Glu (c.1677T>A) is classified Uncertain significance in CCSER2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-17). AlphaMissense: ambiguous (0.4994); Absent from gnomAD v4.1.

How common is CCSER2 p.Asp559Glu (c.1677T>A) in the general population?

CCSER2 p.Asp559Glu (c.1677T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCSER2 p.Asp559Glu (c.1677T>A)?

AlphaMissense predicts ambiguous (score 0.4994) — an in-silico prediction, not a clinical call.

CCSER2 p.Asp559Glu

c.1677T>A · rs2493368458 · VCV2326255

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4994	ambiguous
REVEL	0.134	moderately benign-leaning
SaProt	LLR -6.70	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.85	GERP -5.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 143 kb · p 0.88 · regional, not allelic
Overall
CADD	22.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCSER2
Protein: p.Asp559Glu
Coding: c.1677T>A
MANE Select: NM_001284240
dbSNP: rs2493368458
Type: single nucleotide variant
Location: chr10:84417833 (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 p.Asp559Gly Uncertain significance ★ ⚠ same residue
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

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-asp559glu (accessed [today's date]).

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