Is CCSER2 p.Pro631Thr (c.1891C>A) pathogenic?

CCSER2 p.Pro631Thr (c.1891C>A) is classified Uncertain significance in CCSER2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: likely benign (0.1012); Ultra-rare (popmax 0.0816%, sas).

How common is CCSER2 p.Pro631Thr (c.1891C>A) in the general population?

CCSER2 p.Pro631Thr (c.1891C>A) is ultra-rare (popmax 0.0816%, sas) (gnomAD).

What do computational predictors say about CCSER2 p.Pro631Thr (c.1891C>A)?

AlphaMissense predicts likely benign (score 0.1012) — an in-silico prediction, not a clinical call.

CCSER2 p.Pro631Thr

c.1891C>A · rs563138001 · VCV2404385

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1012 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0816%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1012	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -7.90	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 4	GERP 2.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 143 kb · p 0.88 · regional, not allelic
Overall
CADD	23.9	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 0.0816% South Asian · 74/90,642 alleles

Filtering AF 0.0666% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0611%

Overall 0.00465% 75/1,611,270 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0816%	1,225
European (non-Finnish)	8.49e-05%	1,178,310

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.Pro631Thr
Coding: c.1891C>A
MANE Select: NM_001284240
dbSNP: rs563138001
Type: single nucleotide variant
Location: chr10:84438534 (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.Pro631Ala 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-pro631thr (accessed [today's date]).

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