Is C1QL4 p.Pro50Ser (c.148C>T) pathogenic?

C1QL4 p.Pro50Ser (c.148C>T) is classified Likely benign in C1QL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely benign (0.0703); Ultra-rare (popmax 0.0254%, mid).

How common is C1QL4 p.Pro50Ser (c.148C>T) in the general population?

C1QL4 p.Pro50Ser (c.148C>T) is ultra-rare (popmax 0.0254%, mid) (gnomAD).

What do computational predictors say about C1QL4 p.Pro50Ser (c.148C>T)?

AlphaMissense predicts likely benign (score 0.0703) — an in-silico prediction, not a clinical call.

C1QL4 p.Pro50Ser

c.148C>T · VCV3483383

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0703 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0703	likely benign
REVEL	0.31	indeterminate
SaProt	LLR -6.62	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -0.75, phastCons 0.002
Regional constraint	o/e 1.01	unconstrained · MANE · 3,420 bp · p 0.78 · regional, not allelic
Overall
CADD	7.439	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 0.0254% Middle Eastern · 1/3,930 alleles

Filtering AF 0.00593% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0043%

Overall 0.000844% 12/1,422,288 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0254%	3,930
South Asian	0.012%	8,358
Admixed American	0.00309%	32,414
African / African-American	0.0015%	66,530
European (non-Finnish)	9.11e-05%	1,097,726

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.Pro50Ser
Coding: c.148C>T
MANE Select: NM_001008223
Type: single nucleotide variant
Location: chr12:49336330 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI 0.27 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 50: 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-pro50ser (accessed [today's date]).

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