Is CACYBP p.Gln7His (c.21G>C) pathogenic?

CACYBP p.Gln7His (c.21G>C) is classified Uncertain significance in CACYBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.3041); Very rare (popmax 0.000171%, nfe).

How common is CACYBP p.Gln7His (c.21G>C) in the general population?

CACYBP p.Gln7His (c.21G>C) is very rare (popmax 0.000171%, nfe) (gnomAD).

What do computational predictors say about CACYBP p.Gln7His (c.21G>C)?

AlphaMissense predicts likely benign (score 0.3041) — an in-silico prediction, not a clinical call.

CACYBP p.Gln7His

c.21G>C · VCV4218120

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3041 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3041	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -8.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.25	acceptor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 2.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 9,895 bp · p 1.4e-09 · regional, not allelic
Overall
CADD	23.2	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 0.000171% European (non-Finnish) · 2/1,167,036 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00014% 2/1,430,676 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: CACYBP
Protein: p.Gln7His
Coding: c.21G>C
MANE Select: NM_014412
Type: single nucleotide variant
Location: chr1:175004619 (GRCh38)
Gene constraint: LOEUF 1.441 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.05 · 3 PDB
Residue 7: an α-helix; the 'interaction with siah1' region

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

Similar variants

CACYBP p.Thr109= Benign ★★ same type
CACYBP p.Arg208Gln Uncertain significance ★ ⚠ same type
CACYBP p.Arg26Gly Uncertain significance ★ ⚠ same type
CACYBP p.Glu184Gly Uncertain significance ★ ⚠ same type
CACYBP p.Glu227Gly Uncertain significance ★ ⚠ same type
CACYBP p.Ile152Thr Uncertain significance ★ ⚠ same type
CACYBP p.Leu120Pro Uncertain significance ★ ⚠ same type
CACYBP p.Leu55Phe 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/cacybp-p-gln7his (accessed [today's date]).

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