Is C2CD6 p.Asn1083Ser (c.3248A>G) pathogenic?

C2CD6 p.Asn1083Ser (c.3248A>G) is classified Uncertain significance in C2CD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-21). Ultra-rare (popmax 0.0121%, amr).

How common is C2CD6 p.Asn1083Ser (c.3248A>G) in the general population?

C2CD6 p.Asn1083Ser (c.3248A>G) is ultra-rare (popmax 0.0121%, amr) (gnomAD).

C2CD6 p.Asn1083Ser

c.3248A>G · rs975615290 · VCV3135949

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.021	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.43	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -0.54	GERP -4
Regional constraint	o/e 0.80	unconstrained · MANE · 49 kb · p 7.7e-16 · regional, not allelic
Overall
CADD	0.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% Admixed American · 6/49,708 alleles

Filtering AF 0.00522% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00354%

Overall 0.000436% 6/1,377,540 alleles · ultra-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: C2CD6
Protein: p.Asn1083Ser
Coding: c.3248A>G
MANE Select: NM_001168221
dbSNP: rs975615290
Type: single nucleotide variant
Location: chr2:201493093 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 39.82

Full C2CD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C2CD6 p.Ala1682Thr Uncertain significance ★ same type
C2CD6 p.Ala427Gly Uncertain significance ★ ⚠ same type
C2CD6 p.Ala54Pro Uncertain significance ★ ⚠ same type
C2CD6 p.Ala54Ser Uncertain significance ★ ⚠ same type
C2CD6 p.Ala646Ser Uncertain significance ★ same type
C2CD6 p.Ala827Asp Uncertain significance ★ same type
C2CD6 p.Arg1134Cys Uncertain significance ★ same type
C2CD6 p.Arg1134His 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/c2cd6-p-asn1083ser (accessed [today's date]).

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