Is C1QA p.Trp7Arg (c.19T>C) pathogenic?

C1QA p.Trp7Arg (c.19T>C) is classified Uncertain significance in C1QA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-15). AlphaMissense: ambiguous (0.5592); Very rare (popmax 0.00441%, nfe).

How common is C1QA p.Trp7Arg (c.19T>C) in the general population?

C1QA p.Trp7Arg (c.19T>C) is very rare (popmax 0.00441%, nfe) (gnomAD).

What do computational predictors say about C1QA p.Trp7Arg (c.19T>C)?

AlphaMissense predicts ambiguous (score 0.5592) — an in-silico prediction, not a clinical call.

C1QA p.Trp7Arg

c.19T>C · rs775735381 · VCV1431072

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5592 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5592	ambiguous
REVEL	0.724	pathogenic-leaning
SaProt	LLR -5.77	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 1,787 bp · p 0.003 · regional, not allelic
Overall
CADD	25.3	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 0.00441% European (non-Finnish) · 52/1,179,992 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00335% 54/1,613,960 alleles · very rare exomes 53/1,461,814 · genomes 1/152,146 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00441%	22,692
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00133%	74,910

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.Trp7Arg
Coding: c.19T>C
MANE Select: NM_015991
dbSNP: rs775735381
Type: single nucleotide variant
Location: chr1:22637635 (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.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
C1QA p.Arg44Gln 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-trp7arg (accessed [today's date]).

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