Is CCSER1 p.Ser9Pro (c.25T>C) pathogenic?

CCSER1 p.Ser9Pro (c.25T>C) is classified Uncertain significance in CCSER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-08). AlphaMissense: likely pathogenic (0.7031); Very rare (popmax 0.00268%, afr).

How common is CCSER1 p.Ser9Pro (c.25T>C) in the general population?

CCSER1 p.Ser9Pro (c.25T>C) is very rare (popmax 0.00268%, afr) (gnomAD).

What do computational predictors say about CCSER1 p.Ser9Pro (c.25T>C)?

AlphaMissense predicts likely pathogenic (score 0.7031) — an in-silico prediction, not a clinical call.

CCSER1 p.Ser9Pro

c.25T>C · VCV4222324

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7031 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7031	likely pathogenic
REVEL	0.138	moderately benign-leaning
SaProt	LLR -7.21	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1.7, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,291 kb · p 0.093 · regional, not allelic
Overall
CADD	24.2	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 0.00268% African / African-American · 2/74,668 alleles

Filtering AF 0.00115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000979%

Overall 0.00144% 23/1,593,174 alleles · very rare exomes 21/1,441,008 · genomes 2/152,166 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00268%	37,334
European (non-Finnish)	0.0018%	55,683

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: CCSER1
Protein: p.Ser9Pro
Coding: c.25T>C
MANE Select: NM_001145065
Type: single nucleotide variant
Location: chr4:90308309 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 47.56
Residue 9: the 'disordered' region

Full CCSER1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCSER1 p.Val734Ala Benign ★★ same type
CCSER1 p.Ala238Val Uncertain significance ★ ⚠ same type
CCSER1 p.Ala353Val Uncertain significance ★ ⚠ same type
CCSER1 p.Ala357Thr Uncertain significance ★ ⚠ same type
CCSER1 p.Ala440Val Uncertain significance ★ ⚠ same type
CCSER1 p.Ala589Pro Uncertain significance ★ ⚠ same type
CCSER1 p.Ala707Pro Uncertain significance ★ ⚠ same type
CCSER1 p.Ala823Thr 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/ccser1-p-ser9pro (accessed [today's date]).

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