Is C1QB p.Phe72Val (c.214T>G) pathogenic?

C1QB p.Phe72Val (c.214T>G) is classified Uncertain significance in C1QB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-25). AlphaMissense: likely benign (0.1245); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with C1QB p.Phe72Val (c.214T>G)?

C1QB p.Phe72Val (c.214T>G) is associated with Inborn genetic diseases (ClinVar).

How common is C1QB p.Phe72Val (c.214T>G) in the general population?

C1QB p.Phe72Val (c.214T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C1QB p.Phe72Val (c.214T>G)?

AlphaMissense predicts likely benign (score 0.1245) — an in-silico prediction, not a clinical call.

C1QB p.Phe72Val

c.214T>G · VCV3826169

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1245 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1245	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -4.30	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 1.3	GERP -1.2, phastCons 0.47
Regional constraint	o/e 0.86	unconstrained · MANE · 1,920 bp · p 0.012 · regional, not allelic
Overall
CADD	10.85	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 F74V vs ClinVar F72V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: C1QB
Protein: p.Phe72Val
Coding: c.214T>G
MANE Select: NM_001378156
Type: single nucleotide variant
Location: chr1:22660844 (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 72: the collagen-like 1 domain; the collagen-like 2 domain; the 'disordered' region

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.Phe72= Likely benign ★ 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-phe72val (accessed [today's date]).

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