Is C1QL2 p.Pro92Leu (c.275C>T) pathogenic?

C1QL2 p.Pro92Leu (c.275C>T) is classified Uncertain significance in C1QL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.1803); Absent from gnomAD v4.1.

How common is C1QL2 p.Pro92Leu (c.275C>T) in the general population?

C1QL2 p.Pro92Leu (c.275C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C1QL2 p.Pro92Leu (c.275C>T)?

AlphaMissense predicts likely benign (score 0.1803) — an in-silico prediction, not a clinical call.

C1QL2 p.Pro92Leu

c.275C>T · VCV4647120

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1803 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,521,456)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1803	likely benign
REVEL	0.569	indeterminate
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,293 bp · p 0.32 · regional, not allelic
Overall
CADD	27.5	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

No allele count reported in gnomAD v4.1 (AN 1,521,456). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: C1QL2
Protein: p.Pro92Leu
Coding: c.275C>T
MANE Select: NM_182528
Type: single nucleotide variant
Location: chr2:119157995 (GRCh38)
Gene constraint: LOEUF 1.421 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.90
Residue 92: 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.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.Arg90Gln Uncertain significance ★ ⚠ same type
C1QL2 p.Arg90Gly Uncertain significance ★ ⚠ same type
C1QL2 p.Asp34Tyr 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-pro92leu (accessed [today's date]).

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