Is C1QA p.Arg5Gln (c.14G>A) pathogenic?

C1QA p.Arg5Gln (c.14G>A) is classified Uncertain significance in C1QA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). AlphaMissense: likely benign (0.0917); Very rare (popmax 0.00329%, sas).

How common is C1QA p.Arg5Gln (c.14G>A) in the general population?

C1QA p.Arg5Gln (c.14G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about C1QA p.Arg5Gln (c.14G>A)?

AlphaMissense predicts likely benign (score 0.0917) — an in-silico prediction, not a clinical call.

C1QA p.Arg5Gln

c.14G>A · rs1435120957 · VCV2176737

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0917 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0917	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -8.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.24	GERP -2.1, phastCons 0.003
Regional constraint	o/e 0.84	unconstrained · MANE · 1,787 bp · p 0.003 · regional, not allelic
Overall
CADD	8.455	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 0.00329% South Asian · 3/91,072 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00112% 18/1,613,948 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,357
Remaining individualsnot grpmax-eligible	0.0032%	31,243
Admixed American	0.00167%	59,994
European (non-Finnish)	0.00102%	98,332

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.Arg5Gln
Coding: c.14G>A
MANE Select: NM_015991
dbSNP: rs1435120957
Type: single nucleotide variant
Location: chr1:22637630 (GRCh38)
Gene constraint: LOEUF 0.997 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 83.68 · 11 PDB

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

Similar variants

C1QA p.Arg5Trp Uncertain significance ★ ⚠ 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
C1QA p.Arg42Gln 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-arg5gln (accessed [today's date]).

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