Is CCSER1 p.Leu552Pro (c.1655T>C) pathogenic?

CCSER1 p.Leu552Pro (c.1655T>C) is classified Uncertain significance in CCSER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-18). AlphaMissense: likely benign (0.3301); Absent from gnomAD v4.1.

How common is CCSER1 p.Leu552Pro (c.1655T>C) in the general population?

CCSER1 p.Leu552Pro (c.1655T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCSER1 p.Leu552Pro (c.1655T>C)?

AlphaMissense predicts likely benign (score 0.3301) — an in-silico prediction, not a clinical call.

CCSER1 p.Leu552Pro

c.1655T>C · VCV3997829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3301 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3301	likely benign
REVEL	0.222	benign-leaning
SaProt	LLR -5.34	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 5.5	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,291 kb · p 0.093 · regional, not allelic
Overall
CADD	22.5	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

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: CCSER1
Protein: p.Leu552Pro
Coding: c.1655T>C
MANE Select: NM_001145065
Type: single nucleotide variant
Location: chr4:90468285 (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.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-leu552pro (accessed [today's date]).

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