Is C1QL4 p.Pro10Arg (c.29C>G) pathogenic?

C1QL4 p.Pro10Arg (c.29C>G) is classified Uncertain significance in C1QL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-14). AlphaMissense: likely pathogenic (0.9629); Very rare (popmax 0.00233%, sas).

How common is C1QL4 p.Pro10Arg (c.29C>G) in the general population?

C1QL4 p.Pro10Arg (c.29C>G) is very rare (popmax 0.00233%, sas) (gnomAD).

What do computational predictors say about C1QL4 p.Pro10Arg (c.29C>G)?

AlphaMissense predicts likely pathogenic (score 0.9629) — an in-silico prediction, not a clinical call.

C1QL4 p.Pro10Arg

c.29C>G · rs1378511389 · VCV3135732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9629 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00233%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9629	likely pathogenic
REVEL	0.549	indeterminate
SaProt	LLR -7.82	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 3,420 bp · p 0.78 · regional, not allelic
Overall
CADD	26.9	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 0.00233% South Asian · 2/85,944 alleles

Filtering AF 0.000386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000145%

Overall 0.000143% 2/1,396,798 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: C1QL4
Protein: p.Pro10Arg
Coding: c.29C>G
MANE Select: NM_001008223
dbSNP: rs1378511389
Type: single nucleotide variant
Location: chr12:49336449 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI 0.27 (gnomAD)
Structure: AlphaFold pLDDT 81.51

Full C1QL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C1QL4 p.Ala114Gly Uncertain significance ★ ⚠ same type
C1QL4 p.Ala114Val Uncertain significance ★ ⚠ same type
C1QL4 p.Ala141Glu Uncertain significance ★ same type
C1QL4 p.Ala182Asp Uncertain significance ★ ⚠ same type
C1QL4 p.Arg109Cys Uncertain significance ★ ⚠ same type
C1QL4 p.Arg17His Uncertain significance ★ ⚠ same type
C1QL4 p.Arg38His Uncertain significance ★ ⚠ same type
C1QL4 p.Arg38Leu 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/c1ql4-p-pro10arg (accessed [today's date]).

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