Is CCSER1 p.Ala707Pro (c.2119G>C) pathogenic?

CCSER1 p.Ala707Pro (c.2119G>C) is classified Uncertain significance in CCSER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-31). AlphaMissense: likely pathogenic (0.5748); Very rare (popmax 0.00489%, eas).

How common is CCSER1 p.Ala707Pro (c.2119G>C) in the general population?

CCSER1 p.Ala707Pro (c.2119G>C) is very rare (popmax 0.00489%, eas) (gnomAD).

What do computational predictors say about CCSER1 p.Ala707Pro (c.2119G>C)?

AlphaMissense predicts likely pathogenic (score 0.5748) — an in-silico prediction, not a clinical call.

CCSER1 p.Ala707Pro

c.2119G>C · VCV3487637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5748 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00489%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5748	likely pathogenic
REVEL	0.167	moderately benign-leaning
SaProt	LLR -11.37	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,291 kb · p 0.093 · regional, not allelic
Overall
CADD	23.4	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 0.00489% East Asian · 2/40,904 alleles

Filtering AF 0.00081% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000303%

Overall 0.000143% 2/1,399,166 alleles · very rare

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.Ala707Pro
Coding: c.2119G>C
MANE Select: NM_001145065
Type: single nucleotide variant
Location: chr4:90923394 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 47.56

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.Ala823Thr Uncertain significance ★ ⚠ same type
CCSER1 p.Arg14Trp 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-ala707pro (accessed [today's date]).

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