Is C1QL1 p.Pro60Arg (c.179C>G) pathogenic?

C1QL1 p.Pro60Arg (c.179C>G) is classified Uncertain significance in C1QL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: likely benign (0.125); Very rare (popmax 0.00211%, nfe).

How common is C1QL1 p.Pro60Arg (c.179C>G) in the general population?

C1QL1 p.Pro60Arg (c.179C>G) is very rare (popmax 0.00211%, nfe) (gnomAD).

What do computational predictors say about C1QL1 p.Pro60Arg (c.179C>G)?

AlphaMissense predicts likely benign (score 0.125) — an in-silico prediction, not a clinical call.

C1QL1 p.Pro60Arg

c.179C>G · rs1160311746 · VCV3135717

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.125 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00211%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.125	likely benign
REVEL	0.251	benign-leaning
SaProt	LLR -7.80	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 11	GERP -0.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 7,857 bp · p 0.079 · regional, not allelic
Overall
CADD	23.5	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

Grpmax group 0.00211% European (non-Finnish) · 22/1,041,330 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00118%

Overall 0.00183% 24/1,312,994 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00404%	24,741
European (non-Finnish)grpmax	0.00211%	47,333

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: C1QL1
Protein: p.Pro60Arg
Coding: c.179C>G
MANE Select: NM_006688
dbSNP: rs1160311746
Type: single nucleotide variant
Location: chr17:44967870 (GRCh38)
Gene constraint: LOEUF 1.723 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.26
Residue 60: the 'disordered' region

Full C1QL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C1QL1 p.Ala113Val Uncertain significance ★ ⚠ same type
C1QL1 p.Ala131Thr Uncertain significance ★ ⚠ same type
C1QL1 p.Ala204Ser Uncertain significance ★ ⚠ same type
C1QL1 p.Ala226Pro Uncertain significance ★ ⚠ same type
C1QL1 p.Ala42Thr Uncertain significance ★ ⚠ same type
C1QL1 p.Arg29Leu Uncertain significance ★ ⚠ same type
C1QL1 p.Arg38Leu Uncertain significance ★ ⚠ same type
C1QL1 p.Asp186Gly 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/c1ql1-p-pro60arg (accessed [today's date]).

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