Is C1QL3 p.Leu152= (c.456C>T) pathogenic?

C1QL3 p.Leu152= (c.456C>T) is classified Benign in C1QL3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-12). Common (popmax 9.15%, afr) — too common for a highly-penetrant pathogenic allele.

C1QL3 p.Leu152=

Q: How common is C1QL3 p.Leu152= (c.456C>T) in the general population?

C1QL3 p.Leu152= (c.456C>T) is common (popmax 9.15%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.456C>T · rs75810014 · VCV780849

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 9.15%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.78	GERP -1.2
Overall
CADD	7.163	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.15% African / African-American · 6,858/74,946 alleles

Filtering AF 8.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.9%

Overall 0.499% 8,060/1,613,704 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.15%	11
Admixed American	0.72%	139
Remaining individualsnot grpmax-eligible	0.592%	169
Middle Eastern	0.429%	233
European (non-Finnish)	0.0304%	3,286
South Asian	0.0165%	6,071

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.Leu152=
Coding: c.456C>T
MANE Select: NM_001010908
dbSNP: rs75810014
Type: single nucleotide variant
Location: chr10:16520610 (GRCh38)
Gene constraint: LOEUF 0.788 · pLI 0.54 (gnomAD)
Structure: AlphaFold pLDDT 80.16
Residue 152: the c1q domain

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

Similar variants

C1QL3 p.Ala40Val Uncertain significance ★ ⚠ same type
C1QL3 p.Arg98Pro 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-leu152 (accessed [today's date]).

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