Is C1QL3 p.Arg98Pro (c.293G>C) pathogenic?

C1QL3 p.Arg98Pro (c.293G>C) is classified Uncertain significance in C1QL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-15). AlphaMissense: likely benign (0.1316); Ultra-rare (popmax 0.0252%, mid).

How common is C1QL3 p.Arg98Pro (c.293G>C) in the general population?

C1QL3 p.Arg98Pro (c.293G>C) is ultra-rare (popmax 0.0252%, mid) (gnomAD).

What do computational predictors say about C1QL3 p.Arg98Pro (c.293G>C)?

AlphaMissense predicts likely benign (score 0.1316) — an in-silico prediction, not a clinical call.

C1QL3 p.Arg98Pro

c.293G>C · VCV3483379

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1316 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0252%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1316	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -3.90	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 4.7	GERP -1.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 6,368 bp · p 0.003 · regional, not allelic
Overall
CADD	22.6	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 0.0252% Middle Eastern · 1/3,970 alleles

Filtering AF 0.00978% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00914%

Overall 0.0104% 136/1,304,962 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0252%	3,970
Admixed American	0.0126%	7,910
Remaining individualsnot grpmax-eligible	0.0125%	8,013
European (non-Finnish)	0.0115%	8,696
South Asian	0.0101%	9,937
African / African-American	0.00467%	21,423
Finnishnot grpmax-eligible	0.00208%	48,012

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: C1QL3
Protein: p.Arg98Pro
Coding: c.293G>C
MANE Select: NM_001010908
Type: single nucleotide variant
Location: chr10:16520773 (GRCh38)
Gene constraint: LOEUF 0.788 · pLI 0.54 (gnomAD)
Structure: AlphaFold pLDDT 80.16
Residue 98: the collagen-like domain; the 'disordered' region

Full C1QL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C1QL3 p.Leu152= Benign ★★ same type
C1QL3 p.Ala40Val Uncertain significance ★ ⚠ same type
C1QL3 p.Asn111Lys Uncertain significance ★ ⚠ same type
C1QL3 p.Asp48His Uncertain significance ★ ⚠ same type
C1QL3 p.Gln99Pro Uncertain significance ★ ⚠ same type
C1QL3 p.Glu23Lys Uncertain significance ★ ⚠ same type
C1QL3 p.Glu92Gln Uncertain significance ★ ⚠ same type
C1QL3 p.Gly109Asp 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/c1ql3-p-arg98pro (accessed [today's date]).

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