Is C4B p.Arg1352Ser (c.4054C>A) pathogenic?

C4B p.Arg1352Ser (c.4054C>A) is classified Uncertain significance in C4B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-09). AlphaMissense: likely benign (0.1173); Absent from gnomAD v4.1.

How common is C4B p.Arg1352Ser (c.4054C>A) in the general population?

C4B p.Arg1352Ser (c.4054C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C4B p.Arg1352Ser (c.4054C>A)?

AlphaMissense predicts likely benign (score 0.1173) — an in-silico prediction, not a clinical call.

C4B p.Arg1352Ser

c.4054C>A · rs1435006597 · VCV2259572

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1173 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1173	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -5.69	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 0.18	GERP -1.9
Overall
CADD	4.526	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.Arg1352Ser
Coding: c.4054C>A
MANE Select: NM_007293 · reported on NM_001002029
dbSNP: rs1435006597
Type: single nucleotide variant
Location: chr6:32030025 (GRCh38)
Structure: AlphaFold pLDDT 83.56 · 12 PDB

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

Similar variants

C4B p.Arg1352Cys Uncertain significance ★ ⚠ same residue
C4B p.Arg1352Leu Uncertain significance ★ ⚠ same residue
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

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-arg1352ser (accessed [today's date]).

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