Is CCDC85C p.Pro338Arg (c.1013C>G) pathogenic?

CCDC85C p.Pro338Arg (c.1013C>G) is classified Uncertain significance in CCDC85C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.1407); Very rare (popmax 0.00393%, amr).

How common is CCDC85C p.Pro338Arg (c.1013C>G) in the general population?

CCDC85C p.Pro338Arg (c.1013C>G) is very rare (popmax 0.00393%, amr) (gnomAD).

What do computational predictors say about CCDC85C p.Pro338Arg (c.1013C>G)?

AlphaMissense predicts likely benign (score 0.1407) — an in-silico prediction, not a clinical call.

CCDC85C p.Pro338Arg

c.1013C>G · VCV4649743

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1407 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00393%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1407	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -6.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 88 kb · p 0.57 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00393% Admixed American · 2/50,938 alleles

Filtering AF 0.000651% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000244%

Overall 0.000968% 15/1,550,008 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00393%	25,469
Remaining individualsnot grpmax-eligible	0.00333%	30,025
African / African-American	0.00274%	36,517
South Asian	0.00119%	84,034
European (non-Finnish)	0.000698%	143,344

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.Pro338Arg
Coding: c.1013C>G
MANE Select: NM_001144995
Type: single nucleotide variant
Location: chr14:99517146 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.38
Residue 338: the 'disordered' region

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

Similar variants

CCDC85C p.Pro338= Likely benign ★ 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-pro338arg (accessed [today's date]).

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