Is C1QL4 p.Pro80His (c.239C>A) pathogenic?

C1QL4 p.Pro80His (c.239C>A) is classified Uncertain significance in C1QL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-11). AlphaMissense: likely benign (0.2327); Absent from gnomAD v4.1.

How common is C1QL4 p.Pro80His (c.239C>A) in the general population?

C1QL4 p.Pro80His (c.239C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C1QL4 p.Pro80His (c.239C>A)?

AlphaMissense predicts likely benign (score 0.2327) — an in-silico prediction, not a clinical call.

C1QL4 p.Pro80His

c.239C>A · VCV3483390

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2327 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,469,772)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2327	likely benign
REVEL	0.647	pathogenic-leaning
SaProt	LLR -9.85	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 3,420 bp · p 0.78 · regional, not allelic
Overall
CADD	24.9	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

No allele count reported in gnomAD v4.1 (AN 1,469,772). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: C1QL4
Protein: p.Pro80His
Coding: c.239C>A
MANE Select: NM_001008223
Type: single nucleotide variant
Location: chr12:49336239 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI 0.27 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 80: the collagen-like domain; the 'disordered' region

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-pro80his (accessed [today's date]).

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