Is C4B p.Met841Val (c.2521A>G) pathogenic?

C4B p.Met841Val (c.2521A>G) is classified Likely benign in C4B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: likely benign (0.0468); Very rare (popmax 0.00238%, eas).

How common is C4B p.Met841Val (c.2521A>G) in the general population?

C4B p.Met841Val (c.2521A>G) is very rare (popmax 0.00238%, eas) (gnomAD).

What do computational predictors say about C4B p.Met841Val (c.2521A>G)?

AlphaMissense predicts likely benign (score 0.0468) — an in-silico prediction, not a clinical call.

C4B p.Met841Val

c.2521A>G · rs1258461979 · VCV3136007

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0468 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00238%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0468	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -2.96	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 -15	GERP -4
Overall
CADD	0.001	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

Grpmax group 0.00238% East Asian · 1/42,082 alleles

Overall 7.15e-05% 1/1,399,106 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: C4B
Protein: p.Met841Val
Coding: c.2521A>G
MANE Select: NM_007293 · reported on NM_001002029
dbSNP: rs1258461979
Type: single nucleotide variant
Location: chr6:32027051 (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 p.Met841Ile 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
C4B c.3676+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-met841val (accessed [today's date]).

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