Is CCDC85C p.Pro4Leu (c.11C>T) pathogenic?

CCDC85C p.Pro4Leu (c.11C>T) is classified Uncertain significance in CCDC85C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: ambiguous (0.3799); Very rare (popmax 0.00223%, nfe).

How common is CCDC85C p.Pro4Leu (c.11C>T) in the general population?

CCDC85C p.Pro4Leu (c.11C>T) is very rare (popmax 0.00223%, nfe) (gnomAD).

What do computational predictors say about CCDC85C p.Pro4Leu (c.11C>T)?

AlphaMissense predicts ambiguous (score 0.3799) — an in-silico prediction, not a clinical call.

CCDC85C p.Pro4Leu

c.11C>T · VCV4649745

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3799 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3799	ambiguous
REVEL	0.03	moderately benign-leaning
SaProt	LLR -7.81	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 4.1	GERP -0.68, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 597 bp · p 0.026 · regional, not allelic
Overall
CADD	20.2	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 0.00223% European (non-Finnish) · 24/1,074,988 alleles

Filtering AF 0.00151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00127%

Overall 0.00181% 25/1,384,194 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00223%	44,791
Remaining individualsnot grpmax-eligible	0.0019%	52,734

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.Pro4Leu
Coding: c.11C>T
MANE Select: NM_001144995
Type: single nucleotide variant
Location: chr14:99603949 (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.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
CCDC85C p.Ala157Val 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-pro4leu (accessed [today's date]).

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