Is C2CD4D p.Thr100Lys (c.299C>A) pathogenic?

C2CD4D p.Thr100Lys (c.299C>A) is classified Uncertain significance in C2CD4D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely pathogenic (0.8899); Absent from gnomAD v4.1.

How common is C2CD4D p.Thr100Lys (c.299C>A) in the general population?

C2CD4D p.Thr100Lys (c.299C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C2CD4D p.Thr100Lys (c.299C>A)?

AlphaMissense predicts likely pathogenic (score 0.8899) — an in-silico prediction, not a clinical call.

C2CD4D p.Thr100Lys

c.299C>A · VCV3483569

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8899 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,374,606)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8899	likely pathogenic · top 3% in C2CD4D
REVEL	0.448	indeterminate
SaProt	LLR -5.58	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Overall
CADD	27.6	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

No allele count reported in gnomAD v4.1 (AN 1,374,606). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: C2CD4D
Protein: p.Thr100Lys
Coding: c.299C>A
MANE Select: NM_001394591
Type: single nucleotide variant
Location: chr1:151838691 (GRCh38)
Gene constraint: LOEUF 1.931 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 66.41

Full C2CD4D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C2CD4D p.Ala120Val Uncertain significance ★ ⚠ same type
C2CD4D p.Ala301Gly Uncertain significance ★ ⚠ same type
C2CD4D p.Ala31Ser Uncertain significance ★ ⚠ same type
C2CD4D p.Ala38Pro Uncertain significance ★ ⚠ same type
C2CD4D p.Ala63Glu Uncertain significance ★ ⚠ same type
C2CD4D p.Ala78Thr Uncertain significance ★ ⚠ same type
C2CD4D p.Arg102Trp Uncertain significance ★ ⚠ same type
C2CD4D p.Arg185His 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/c2cd4d-p-thr100lys (accessed [today's date]).

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