Is C2CD3 p.Ser1885Pro (c.5653T>C) pathogenic?

C2CD3 p.Ser1885Pro (c.5653T>C) is classified Conflicting classifications of pathogenicity in C2CD3 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-06-01). AlphaMissense: ambiguous (0.526); Rare (popmax 0.62%, nfe).

How common is C2CD3 p.Ser1885Pro (c.5653T>C) in the general population?

C2CD3 p.Ser1885Pro (c.5653T>C) is rare (popmax 0.62%, nfe) (gnomAD).

What do computational predictors say about C2CD3 p.Ser1885Pro (c.5653T>C)?

AlphaMissense predicts ambiguous (score 0.526) — an in-silico prediction, not a clinical call.

C2CD3 p.Ser1885Pro

c.5653T>C · rs142277857 · VCV774697

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

ambiguous

0.526 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.62%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.526	ambiguous
REVEL	0.187	benign-leaning
SaProt	LLR -8.02	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 9.3	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 157 kb · p 9.8e-06 · regional, not allelic
Overall
CADD	25.0	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 0.62% European (non-Finnish) · 7,311/1,179,946 alleles

Filtering AF 0.608% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.603%

Overall 0.475% 7,674/1,613,956 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.62%	161
Remaining individualsnot grpmax-eligible	0.288%	347
Finnishnot grpmax-eligible	0.155%	647
Amishnot grpmax-eligible	0.11%	912
African / African-American	0.0787%	1,271
Admixed American	0.0317%	3,158
Middle Eastern	0.0165%	6,056
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,868
South Asian	0.0011%	91,056

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: C2CD3
Protein: p.Ser1885Pro
Coding: c.5653T>C
MANE Select: NM_001286577
dbSNP: rs142277857
Type: single nucleotide variant
Location: chr11:74042061 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65

Full C2CD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C2CD3 c.3911-2A>T Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Arg621Ter Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Arg666Ter Pathogenic ★★ same type
C2CD3 p.Arg768Ter Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Tyr173Ter Pathogenic/Likely pathogenic ★★ same type
C2CD3 c.2085+5G>A Uncertain significance ★★ same type
C2CD3 c.4951+6C>T Uncertain significance ★★ same type
C2CD3 c.5495+4A>G 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/c2cd3-p-ser1885pro (accessed [today's date]).

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