Is C8B p.Gln80Pro (c.239A>C) pathogenic?

C8B p.Gln80Pro (c.239A>C) is classified Uncertain significance in C8B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: ambiguous (0.433); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with C8B p.Gln80Pro (c.239A>C)?

C8B p.Gln80Pro (c.239A>C) is associated with Inborn genetic diseases (ClinVar).

How common is C8B p.Gln80Pro (c.239A>C) in the general population?

C8B p.Gln80Pro (c.239A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C8B p.Gln80Pro (c.239A>C)?

AlphaMissense predicts ambiguous (score 0.433) — an in-silico prediction, not a clinical call.

C8B p.Gln80Pro

c.239A>C · VCV4217467

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.433 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.433	ambiguous
REVEL	0.266	benign-leaning
SaProt	LLR -7.13	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2.2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 37 kb · p 0.016 · regional, not allelic
Overall
CADD	24.8	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

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: C8B
Protein: p.Gln80Pro
Coding: c.239A>C
MANE Select: NM_000066
Type: single nucleotide variant
Location: chr1:56960030 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.99 · 8 PDB
Residue 80: a disulfide bond; a turn; the tsp type-1 1 domain

Full C8B 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

C8B p.Ala21Thr Uncertain significance ★★ ⚠ same condition
C8B p.Ala446Val Uncertain significance ★★ ⚠ same condition
C8B p.Arg136Cys Uncertain significance ★★ ⚠ same condition
C8B p.Arg136His Uncertain significance ★★ ⚠ same condition
C8B p.Arg156Gly Uncertain significance ★★ ⚠ same condition
C8B p.Arg296Cys Uncertain significance ★★ ⚠ same condition
C8B p.Arg296His Uncertain significance ★★ ⚠ same condition
C8B p.Arg428Gln 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/c8b-p-gln80pro (accessed [today's date]).

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