Is C1QA p.Arg44Trp (c.130C>T) pathogenic?

C1QA p.Arg44Trp (c.130C>T) is classified Uncertain significance in C1QA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-30). AlphaMissense: likely benign (0.1164); Very rare (popmax 0.00267%, afr).

How common is C1QA p.Arg44Trp (c.130C>T) in the general population?

C1QA p.Arg44Trp (c.130C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about C1QA p.Arg44Trp (c.130C>T)?

AlphaMissense predicts likely benign (score 0.1164) — an in-silico prediction, not a clinical call.

C1QA p.Arg44Trp

c.130C>T · VCV4961798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1164 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1164	likely benign
REVEL	0.463	indeterminate
SaProt	LLR -9.51	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 -0.88	GERP -2.5
Regional constraint	o/e 0.84	unconstrained · MANE · 1,787 bp · p 0.003 · regional, not allelic
Overall
CADD	19.99	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 0.00267% African / African-American · 2/74,836 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000312% 5/1,604,340 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,418
East Asian	0.00224%	44,596
European (non-Finnish)	0.00017%	588,090

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: C1QA
Protein: p.Arg44Trp
Coding: c.130C>T
MANE Select: NM_015991
Type: single nucleotide variant
Location: chr1:22637746 (GRCh38)
Gene constraint: LOEUF 0.997 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 83.68 · 11 PDB
Residue 44: the collagen-like domain; the 'disordered' region

Full C1QA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C1QA p.Arg44Gln Uncertain significance ★★ ⚠ same residue
C1QA p.Arg44fs Pathogenic ★ same residue
C1QA p.Arg27Ter Pathogenic/Likely pathogenic ★★ same type
C1QA p.Gln208Ter Pathogenic ★★ same type
C1QA p.Gly157Asp Likely pathogenic ★★ same type
C1QA p.Arg150Gln Uncertain significance ★★ ⚠ same type
C1QA p.Arg180Lys Uncertain significance ★★ ⚠ same type
C1QA p.Arg27Gln 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/c1qa-p-arg44trp (accessed [today's date]).

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