Is C4B p.Leu1187Phe (c.3559C>T) pathogenic?

C4B p.Leu1187Phe (c.3559C>T) is classified Uncertain significance in C4B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-20). AlphaMissense: likely benign (0.0974); Absent from gnomAD v4.1.

How common is C4B p.Leu1187Phe (c.3559C>T) in the general population?

C4B p.Leu1187Phe (c.3559C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C4B p.Leu1187Phe (c.3559C>T)?

AlphaMissense predicts likely benign (score 0.0974) — an in-silico prediction, not a clinical call.

C4B p.Leu1187Phe

c.3559C>T · rs2483291022 · VCV2302681

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0974 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0974	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -7.39	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 0.94	GERP 0.49, phastCons 1
Overall
CADD	22.7	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

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: C4B
Protein: p.Leu1187Phe
Coding: c.3559C>T
MANE Select: NM_007293 · reported on NM_001002029
dbSNP: rs2483291022
Type: single nucleotide variant
Location: chr6:32029221 (GRCh38)
Structure: AlphaFold pLDDT 83.56 · 12 PDB

Full C4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C4A c.2944+55T>C Benign/Likely benign ★★ same type
C4A p.Asp1073Gly Benign/Likely benign ★★ same type
C4A p.Pro1120Thr Likely benign ★★ same type
C4B p.Ser1176Asn Benign ★★ ⚠ same type
C4B p.Thr907Ala Benign/Likely benign ★★ same type
C4B c.3230+1G>A Likely pathogenic ★ same type
C4B c.3676+1G>A Likely pathogenic ★ same type
C4A p.Ala1062Val 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/c4b-p-leu1187phe (accessed [today's date]).

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