Is C1QL1 p.Pro18Leu (c.53C>T) pathogenic?

C1QL1 p.Pro18Leu (c.53C>T) is classified Uncertain significance in C1QL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: likely benign (0.0922); Very rare (popmax 0.00983%, sas).

How common is C1QL1 p.Pro18Leu (c.53C>T) in the general population?

C1QL1 p.Pro18Leu (c.53C>T) is very rare (popmax 0.00983%, sas) (gnomAD).

What do computational predictors say about C1QL1 p.Pro18Leu (c.53C>T)?

AlphaMissense predicts likely benign (score 0.0922) — an in-silico prediction, not a clinical call.

C1QL1 p.Pro18Leu

c.53C>T · rs763732036 · VCV3135720

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0922 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00983%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0922	likely benign
REVEL	0.181	moderately benign-leaning
SaProt	LLR -6.01	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 9.3	GERP 0.43, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 7,857 bp · p 0.079 · regional, not allelic
Overall
CADD	20.6	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 0.00983% South Asian · 6/61,018 alleles

Filtering AF 0.00422% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00291%

Overall 0.000486% 6/1,235,290 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: C1QL1
Protein: p.Pro18Leu
Coding: c.53C>T
MANE Select: NM_006688
dbSNP: rs763732036
Type: single nucleotide variant
Location: chr17:44967996 (GRCh38)
Gene constraint: LOEUF 1.723 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.26

Full C1QL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C1QL1 p.Ala113Val Uncertain significance ★ ⚠ same type
C1QL1 p.Ala131Thr Uncertain significance ★ ⚠ same type
C1QL1 p.Ala204Ser Uncertain significance ★ ⚠ same type
C1QL1 p.Ala226Pro Uncertain significance ★ ⚠ same type
C1QL1 p.Ala42Thr Uncertain significance ★ ⚠ same type
C1QL1 p.Arg29Leu Uncertain significance ★ ⚠ same type
C1QL1 p.Arg38Leu Uncertain significance ★ ⚠ same type
C1QL1 p.Asp186Gly 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/c1ql1-p-pro18leu (accessed [today's date]).

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