Is C1QL2 p.Arg90Gly (c.268C>G) pathogenic?

C1QL2 p.Arg90Gly (c.268C>G) is classified Uncertain significance in C1QL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: likely pathogenic (0.7073); Very rare (popmax 0.000264%, nfe).

How common is C1QL2 p.Arg90Gly (c.268C>G) in the general population?

C1QL2 p.Arg90Gly (c.268C>G) is very rare (popmax 0.000264%, nfe) (gnomAD).

What do computational predictors say about C1QL2 p.Arg90Gly (c.268C>G)?

AlphaMissense predicts likely pathogenic (score 0.7073) — an in-silico prediction, not a clinical call.

C1QL2 p.Arg90Gly

c.268C>G · VCV3993827

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7073 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000264%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7073	likely pathogenic
REVEL	0.653	pathogenic-leaning
SaProt	LLR -9.72	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP -1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,293 bp · p 0.32 · regional, not allelic
Overall
CADD	21.3	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 0.000264% European (non-Finnish) · 3/1,136,864 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000219% 3/1,369,958 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: C1QL2
Protein: p.Arg90Gly
Coding: c.268C>G
MANE Select: NM_182528
Type: single nucleotide variant
Location: chr2:119158002 (GRCh38)
Gene constraint: LOEUF 1.421 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.90
Residue 90: the collagen-like domain; the 'disordered' region

Full C1QL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C1QL2 p.Arg90Gln Uncertain significance ★ ⚠ same residue
C1QL2 p.Ile32= Benign ★★ same type
C1QL2 p.Ala123Val Uncertain significance ★ ⚠ same type
C1QL2 p.Ala126Thr Uncertain significance ★ ⚠ same type
C1QL2 p.Ala16Thr Uncertain significance ★ ⚠ same type
C1QL2 p.Ala8Val Uncertain significance ★ ⚠ same type
C1QL2 p.Asp34Tyr Uncertain significance ★ ⚠ same type
C1QL2 p.Asp80Tyr 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/c1ql2-p-arg90gly (accessed [today's date]).

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