Is C2CD6 p.Ser1301Pro (c.3901T>C) pathogenic?

C2CD6 p.Ser1301Pro (c.3901T>C) is classified Uncertain significance in C2CD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). Very rare (popmax 0.000175%, nfe).

How common is C2CD6 p.Ser1301Pro (c.3901T>C) in the general population?

C2CD6 p.Ser1301Pro (c.3901T>C) is very rare (popmax 0.000175%, nfe) (gnomAD).

C2CD6 p.Ser1301Pro

c.3901T>C · VCV3483614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000175%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.034	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -2.1, phastCons 0.15
Regional constraint	o/e 0.80	unconstrained · MANE · 49 kb · p 7.7e-16 · regional, not allelic
Overall
CADD	19.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000175% European (non-Finnish) · 2/1,144,406 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00013% 2/1,532,894 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: C2CD6
Protein: p.Ser1301Pro
Coding: c.3901T>C
MANE Select: NM_001168221
Type: single nucleotide variant
Location: chr2:201492440 (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-ser1301pro (accessed [today's date]).

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