Is C1QB p.Ala172Thr (c.514G>A) pathogenic?

C1QB p.Ala172Thr (c.514G>A) is classified Uncertain significance in C1QB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-11). AlphaMissense: likely benign (0.1425); Ultra-rare (popmax 0.0117%, amr); Associated with Inborn genetic diseases.

What condition is associated with C1QB p.Ala172Thr (c.514G>A)?

C1QB p.Ala172Thr (c.514G>A) is associated with Inborn genetic diseases (ClinVar).

How common is C1QB p.Ala172Thr (c.514G>A) in the general population?

C1QB p.Ala172Thr (c.514G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about C1QB p.Ala172Thr (c.514G>A)?

AlphaMissense predicts likely benign (score 0.1425) — an in-silico prediction, not a clinical call.

C1QB p.Ala172Thr

c.514G>A · VCV3826168

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1425 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1425	likely benign
REVEL	0.369	indeterminate
SaProt	LLR -7.23	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 12	GERP 0.87, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 1,920 bp · p 0.012 · regional, not allelic
Overall
CADD	22.4	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A174T vs ClinVar A172T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/60,002 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000991% 16/1,613,954 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,572
South Asian	0.0011%	91,076
European (non-Finnish)	0.000678%	147,502

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: C1QB
Protein: p.Ala172Thr
Coding: c.514G>A
MANE Select: NM_001378156
Type: single nucleotide variant
Location: chr1:22661144 (GRCh38)
Gene constraint: LOEUF 1.001 · pLI 0.25 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.87 · 11 PDB
Residue 172: the c1q domain; a β-strand

Full C1QB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

C1QB p.Ala172Val Uncertain significance ★ ⚠ same residue
C1QB p.Arg134Gln Uncertain significance ★★ ⚠ same condition
C1QB p.Arg134Trp Uncertain significance ★★ ⚠ same condition
C1QB p.Arg186Gln Uncertain significance ★★ ⚠ same condition
C1QB p.Asp21Asn Uncertain significance ★★ ⚠ same condition
C1QB p.Asp226Glu Uncertain significance ★★ ⚠ same condition
C1QB p.Asp48Asn Uncertain significance ★★ ⚠ same condition
C1QB p.Asp68Gly Uncertain significance ★★ ⚠ same condition

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/c1qb-p-ala172thr (accessed [today's date]).

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