Is C8B p.Val359Gly (c.1076T>G) pathogenic?

C8B p.Val359Gly (c.1076T>G) is classified Uncertain significance in C8B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-12). AlphaMissense: ambiguous (0.556); Absent from gnomAD v4.1.

How common is C8B p.Val359Gly (c.1076T>G) in the general population?

C8B p.Val359Gly (c.1076T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C8B p.Val359Gly (c.1076T>G)?

AlphaMissense predicts ambiguous (score 0.556) — an in-silico prediction, not a clinical call.

C8B p.Val359Gly

c.1076T>G · rs2101407857 · VCV1405223

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.556 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.556	ambiguous
REVEL	0.512	indeterminate
SaProt	LLR -12.49	damaging
Splicing
SpliceAI	Δ0.20	donor loss, 29 bp away · masked 0 · deltas
Pangolin	Δ0.35	gain · loss 0.23 · SpliceAI calls loss · independent
Constraint at this position
Conservation	phyloP 9.2	GERP 2.1, phastCons 0.99
Regional constraint	o/e 1.09	unconstrained · MANE · 37 kb · p 0.016 · regional, not allelic
Overall
CADD	26.4	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.Val359Gly
Coding: c.1076T>G
MANE Select: NM_000066
dbSNP: rs2101407857
Type: single nucleotide variant
Location: chr1:56945850 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.99 · 8 PDB
Residue 359: a UniProt-annotated variant site (in c8d2); a β-strand; the macpf domain

Full C8B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C8B p.Val359Ile Uncertain significance ★★ ⚠ same residue
C8B p.Arg284Ter Pathogenic ★★ same type
C8B p.Arg428Ter Pathogenic ★★ same type
C8B p.Cys508Ter Pathogenic/Likely pathogenic ★★ same type
C8B p.Gln91Ter Pathogenic/Likely pathogenic ★★ same type
C8B p.Trp9Ter Pathogenic ★★ same type
C8B p.Ala21Thr Uncertain significance ★★ ⚠ same type
C8B p.Ala446Val 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/c8b-p-val359gly (accessed [today's date]).

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