Is CCDC89 p.Arg207Cys (c.619C>T) pathogenic?

CCDC89 p.Arg207Cys (c.619C>T) is classified Uncertain significance in CCDC89 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.2495); Absent from gnomAD v4.1.

How common is CCDC89 p.Arg207Cys (c.619C>T) in the general population?

CCDC89 p.Arg207Cys (c.619C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC89 p.Arg207Cys (c.619C>T)?

AlphaMissense predicts likely benign (score 0.2495) — an in-silico prediction, not a clinical call.

CCDC89 p.Arg207Cys

c.619C>T · VCV4221777

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2495 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,868)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2495	likely benign
REVEL	0.233	benign-leaning
SaProt	LLR -12.52	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 0.77, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 1,121 bp · p 0.047 · regional, not allelic
Overall
CADD	23.3	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 1,613,868). 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: CCDC89
Protein: p.Arg207Cys
Coding: c.619C>T
MANE Select: NM_152723
Type: single nucleotide variant
Location: chr11:85685512 (GRCh38)
Gene constraint: LOEUF 1.287 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.06 · 4 PDB

Full CCDC89 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC89 p.Arg207His Uncertain significance ★ ⚠ same residue
CCDC89 p.Ala114Val Uncertain significance ★ ⚠ same type
CCDC89 p.Ala201Val Uncertain significance ★ ⚠ same type
CCDC89 p.Arg182Trp Uncertain significance ★ ⚠ same type
CCDC89 p.Arg22Cys Uncertain significance ★ ⚠ same type
CCDC89 p.Arg2Lys Uncertain significance ★ ⚠ same type
CCDC89 p.Arg313Gln Uncertain significance ★ ⚠ same type
CCDC89 p.Arg60Met 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/ccdc89-p-arg207cys (accessed [today's date]).

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