Is C1QL2 p.Asp80Tyr (c.238G>T) pathogenic?

C1QL2 p.Asp80Tyr (c.238G>T) is classified Uncertain significance in C1QL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-13). AlphaMissense: ambiguous (0.4734); Very rare (popmax 0.00259%, eas).

How common is C1QL2 p.Asp80Tyr (c.238G>T) in the general population?

C1QL2 p.Asp80Tyr (c.238G>T) is very rare (popmax 0.00259%, eas) (gnomAD).

What do computational predictors say about C1QL2 p.Asp80Tyr (c.238G>T)?

AlphaMissense predicts ambiguous (score 0.4734) — an in-silico prediction, not a clinical call.

C1QL2 p.Asp80Tyr

c.238G>T · rs2466990944 · VCV2304900

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4734 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00259%, eas)

Computational evidence

Protein change
AlphaMissense	0.4734	ambiguous
REVEL	0.529	indeterminate
SaProt	LLR -9.37	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP -0.53, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,293 bp · p 0.32 · regional, not allelic
Overall
CADD	26.4	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 0.00259% East Asian · 1/38,536 alleles

Overall 7.27e-05% 1/1,376,090 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.Asp80Tyr
Coding: c.238G>T
MANE Select: NM_182528
dbSNP: rs2466990944
Type: single nucleotide variant
Location: chr2:119158032 (GRCh38)
Gene constraint: LOEUF 1.421 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.90
Residue 80: 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-asp80tyr (accessed [today's date]).

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