Is C2CD3 p.Val887Met (c.2659G>A) pathogenic?

C2CD3 p.Val887Met (c.2659G>A) is classified Benign/Likely benign in C2CD3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.1073); Rare (popmax 0.647%, nfe); Associated with Inborn genetic diseases.

What condition is associated with C2CD3 p.Val887Met (c.2659G>A)?

C2CD3 p.Val887Met (c.2659G>A) is associated with Inborn genetic diseases (ClinVar).

How common is C2CD3 p.Val887Met (c.2659G>A) in the general population?

C2CD3 p.Val887Met (c.2659G>A) is rare (popmax 0.647%, nfe) (gnomAD).

What do computational predictors say about C2CD3 p.Val887Met (c.2659G>A)?

AlphaMissense predicts likely benign (score 0.1073) — an in-silico prediction, not a clinical call.

C2CD3 p.Val887Met

c.2659G>A · rs117535770 · VCV599458

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1073 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.647%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1073	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.31	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 157 kb · p 9.8e-06 · regional, not allelic
Overall
CADD	16.94	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 0.647% European (non-Finnish) · 7,640/1,179,968 alleles

Filtering AF 0.635% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.63%

Overall 0.557% 8,993/1,614,090 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.932%	107
European (non-Finnish)grpmax	0.647%	154
Ashkenazi Jewishnot grpmax-eligible	0.459%	218
Remaining individualsnot grpmax-eligible	0.389%	257
Admixed American	0.278%	359
South Asian	0.144%	695
African / African-American	0.103%	975
Middle Eastern	0.0165%	6,062
East Asian	0.00223%	44,878

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val887Met
Coding: c.2659G>A
MANE Select: NM_001286577
dbSNP: rs117535770
Type: single nucleotide variant
Location: chr11:74100598 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65
Residue 887: the c2 2 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

C2CD3 p.Val887Leu Uncertain significance ★ ⚠ same residue
C2CD3 c.2085+5G>A Uncertain significance ★★ same condition
C2CD3 c.4951+6C>T Uncertain significance ★★ same condition
C2CD3 p.Ala1382Pro Uncertain significance ★★ ⚠ same condition
C2CD3 p.Ala1777Thr Uncertain significance ★★ ⚠ same condition
C2CD3 p.Ala95Thr Uncertain significance ★★ ⚠ same condition
C2CD3 p.Arg1122Ile Uncertain significance ★★ ⚠ same condition
C2CD3 p.Arg1145His Uncertain significance ★★ ⚠ same condition

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-val887met (accessed [today's date]).

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