Is CCDC85C p.Arg407Trp (c.1219C>T) pathogenic?

CCDC85C p.Arg407Trp (c.1219C>T) is classified Uncertain significance in CCDC85C (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-14). AlphaMissense: likely pathogenic (0.9333); Very rare (popmax 0.00981%, amr).

How common is CCDC85C p.Arg407Trp (c.1219C>T) in the general population?

CCDC85C p.Arg407Trp (c.1219C>T) is very rare (popmax 0.00981%, amr) (gnomAD).

What do computational predictors say about CCDC85C p.Arg407Trp (c.1219C>T)?

AlphaMissense predicts likely pathogenic (score 0.9333) — an in-silico prediction, not a clinical call.

CCDC85C p.Arg407Trp

c.1219C>T · rs895199409 · VCV2380188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9333 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00981%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9333	likely pathogenic
REVEL	0.242	benign-leaning
SaProt	LLR -8.97	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP -0.74, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 88 kb · p 0.57 · regional, not allelic
Overall
CADD	32.0	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 0.00981% Admixed American · 5/50,980 alleles

Filtering AF 0.00382% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00248%

Overall 0.00148% 23/1,550,796 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00981%	10,196
Remaining individualsnot grpmax-eligible	0.00499%	20,025
South Asian	0.00238%	42,035
Finnishnot grpmax-eligible	0.00169%	59,312
European (non-Finnish)	0.00105%	95,569

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: CCDC85C
Protein: p.Arg407Trp
Coding: c.1219C>T
MANE Select: NM_001144995
dbSNP: rs895199409
Type: single nucleotide variant
Location: chr14:99515287 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.38

Full CCDC85C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNK p.Pro407Leu Uncertain significance ★ ⚠ same residue
CCNK p.Pro462Thr Uncertain significance ★★ ⚠ same type
CCNK p.Val333Phe Uncertain significance ★★ ⚠ same type
CCNK p.Pro484= Likely benign ★★ same type
CCDC85C p.Ala102Val Uncertain significance ★ ⚠ same type
CCDC85C p.Ala11Ser Uncertain significance ★ ⚠ same type
CCDC85C p.Ala156Thr Uncertain significance ★ ⚠ same type
CCDC85C p.Ala156Val 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/ccdc85c-p-arg407trp (accessed [today's date]).

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