Is C1QL2 p.Pro70Ser (c.208C>T) pathogenic?

C1QL2 p.Pro70Ser (c.208C>T) is classified Uncertain significance in C1QL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). AlphaMissense: likely benign (0.116); Very rare (popmax 0.00363%, sas).

How common is C1QL2 p.Pro70Ser (c.208C>T) in the general population?

C1QL2 p.Pro70Ser (c.208C>T) is very rare (popmax 0.00363%, sas) (gnomAD).

What do computational predictors say about C1QL2 p.Pro70Ser (c.208C>T)?

AlphaMissense predicts likely benign (score 0.116) — an in-silico prediction, not a clinical call.

C1QL2 p.Pro70Ser

c.208C>T · VCV4217078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.116 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00363%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.116	likely benign
REVEL	0.316	indeterminate
SaProt	LLR -6.27	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 8.4	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,293 bp · p 0.32 · regional, not allelic
Overall
CADD	19.12	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 0.00363% South Asian · 3/82,616 alleles

Filtering AF 0.000964% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000467%

Overall 0.000326% 5/1,531,502 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00363%	27,539
Ashkenazi Jewishnot grpmax-eligible	0.00361%	27,708
African / African-American	0.00143%	69,778

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.Pro70Ser
Coding: c.208C>T
MANE Select: NM_182528
Type: single nucleotide variant
Location: chr2:119158062 (GRCh38)
Gene constraint: LOEUF 1.421 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.90
Residue 70: 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-pro70ser (accessed [today's date]).

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