Is C1QBP p.Ser52Phe (c.155C>T) pathogenic?

C1QBP p.Ser52Phe (c.155C>T) is classified Uncertain significance in C1QBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.1379); Very rare (popmax 0.000175%, nfe); Associated with Inborn genetic diseases.

What condition is associated with C1QBP p.Ser52Phe (c.155C>T)?

C1QBP p.Ser52Phe (c.155C>T) is associated with Inborn genetic diseases (ClinVar).

How common is C1QBP p.Ser52Phe (c.155C>T) in the general population?

C1QBP p.Ser52Phe (c.155C>T) is very rare (popmax 0.000175%, nfe) (gnomAD).

What do computational predictors say about C1QBP p.Ser52Phe (c.155C>T)?

AlphaMissense predicts likely benign (score 0.1379) — an in-silico prediction, not a clinical call.

C1QBP p.Ser52Phe

c.155C>T · VCV4217062

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1379 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000175%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1379	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -8.68	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 8.1	phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 6,055 bp · p 0.32 · regional, not allelic
Overall
CADD	19.88	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 0.000175% European (non-Finnish) · 2/1,141,910 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000144% 2/1,385,210 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: C1QBP
Protein: p.Ser52Phe
Coding: c.155C>T
MANE Select: NM_001212
Type: single nucleotide variant
Location: chr17:5438919 (GRCh38)
Gene constraint: LOEUF 1.155 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.12 · 4 PDB

Full C1QBP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

C1QBP p.Ala81Gly Uncertain significance ★★ ⚠ same condition
C1QBP p.Asn134Ser Uncertain significance ★★ ⚠ same condition
C1QBP p.Glu93Asp Uncertain significance ★★ ⚠ same condition
C1QBP p.Lys179Thr Uncertain significance ★★ ⚠ same condition
C1QBP p.Pro149Ser Uncertain significance ★★ ⚠ same condition
C1QBP p.Ser26Leu Uncertain significance ★★ ⚠ same condition
C1QBP p.Ala181Ser Uncertain significance ★ ⚠ same condition
C1QBP p.Ala22Ser Uncertain significance ★ ⚠ same condition

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/c1qbp-p-ser52phe (accessed [today's date]).

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