Is C1QA p.Pro57Ser (c.169C>T) pathogenic?

C1QA p.Pro57Ser (c.169C>T) is classified Uncertain significance in C1QA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-25). AlphaMissense: likely benign (0.0937); Very rare (popmax 0.00112%, nfe).

How common is C1QA p.Pro57Ser (c.169C>T) in the general population?

C1QA p.Pro57Ser (c.169C>T) is very rare (popmax 0.00112%, nfe) (gnomAD).

What do computational predictors say about C1QA p.Pro57Ser (c.169C>T)?

AlphaMissense predicts likely benign (score 0.0937) — an in-silico prediction, not a clinical call.

C1QA p.Pro57Ser

c.169C>T · rs1484586103 · VCV1897734

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0937 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00112%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0937	likely benign
REVEL	0.311	indeterminate
SaProt	LLR -7.80	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 -2	GERP -3.4
Regional constraint	o/e 0.84	unconstrained · MANE · 1,787 bp · p 0.003 · regional, not allelic
Overall
CADD	5.136	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 0.00112% European (non-Finnish) · 13/1,163,982 alleles

Filtering AF 0.000623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00048%

Overall 0.000822% 13/1,580,666 alleles · very rare

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.Pro57Ser
Coding: c.169C>T
MANE Select: NM_015991
dbSNP: rs1484586103
Type: single nucleotide variant
Location: chr1:22638838 (GRCh38)
Gene constraint: LOEUF 0.997 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 83.68 · 11 PDB
Residue 57: a modified residue (4-hydroxyproline); 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.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-pro57ser (accessed [today's date]).

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