Is C6 p.Asn910Lys (c.2730C>G) pathogenic?

C6 p.Asn910Lys (c.2730C>G) is classified Uncertain significance in C6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-06). AlphaMissense: ambiguous (0.4774); Very rare (popmax 0.00102%, nfe).

How common is C6 p.Asn910Lys (c.2730C>G) in the general population?

C6 p.Asn910Lys (c.2730C>G) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about C6 p.Asn910Lys (c.2730C>G)?

AlphaMissense predicts ambiguous (score 0.4774) — an in-silico prediction, not a clinical call.

C6 p.Asn910Lys

c.2730C>G · rs2150210279 · VCV1515442

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4774 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4774	ambiguous
REVEL	0.163	moderately benign-leaning
SaProt	LLR -6.34	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 2.3	GERP -0.084, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 60 kb · p 0.0034 · regional, not allelic
Overall
CADD	20.8	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

Grpmax group 0.00102% European (non-Finnish) · 12/1,179,564 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000821% 12/1,461,284 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: C6
Protein: p.Asn910Lys
Coding: c.2730C>G
MANE Select: NM_000065
dbSNP: rs2150210279
Type: single nucleotide variant
Location: chr5:41142900 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.72 · 11 PDB
Residue 910: the kazal-like 2 domain; the 'c5b-binding domain' region; the 'factor i module (fim) 2' region; a β-strand; a disulfide bond

Full C6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C6 p.Arg596Ter Pathogenic/Likely pathogenic ★★ same type
C6 p.Arg606Ter Pathogenic ★★ same type
C6 p.Cys218Ter Pathogenic/Likely pathogenic ★★ same type
C6 p.Tyr683Ter Pathogenic/Likely pathogenic ★★ same type
C6 p.Ala21Val Uncertain significance ★★ ⚠ same type
C6 p.Ala396Gly Uncertain significance ★★ ⚠ same type
C6 p.Ala456Thr Uncertain significance ★★ ⚠ same type
C6 p.Ala500Ser 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/c6-p-asn910lys (accessed [today's date]).

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