Is CCDC85B p.Glu23Asp (c.69G>C) pathogenic?

CCDC85B p.Glu23Asp (c.69G>C) is classified Uncertain significance in CCDC85B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely benign (0.1031); Very rare (popmax 0.000525%, nfe).

How common is CCDC85B p.Glu23Asp (c.69G>C) in the general population?

CCDC85B p.Glu23Asp (c.69G>C) is very rare (popmax 0.000525%, nfe) (gnomAD).

What do computational predictors say about CCDC85B p.Glu23Asp (c.69G>C)?

AlphaMissense predicts likely benign (score 0.1031) — an in-silico prediction, not a clinical call.

CCDC85B p.Glu23Asp

c.69G>C · rs1041310286 · VCV2221048

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1031 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000525%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1031	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -8.21	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 1.5, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 605 bp · p 4.6e-05 · regional, not allelic
Overall
CADD	23.5	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 0.000525% European (non-Finnish) · 6/1,142,870 alleles

Filtering AF 0.000189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000124%

Overall 0.000393% 6/1,525,134 alleles · very rare

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: CCDC85B
Protein: p.Glu23Asp
Coding: c.69G>C
MANE Select: NM_006848
dbSNP: rs1041310286
Type: single nucleotide variant
Location: chr11:65890852 (GRCh38)
Gene constraint: LOEUF 1.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.15

Full CCDC85B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC85B p.Ala143Val Uncertain significance ★ ⚠ same type
CCDC85B p.Arg107Gln Uncertain significance ★ ⚠ same type
CCDC85B p.Arg61Leu Uncertain significance ★ ⚠ same type
CCDC85B p.Arg68Gly Uncertain significance ★ ⚠ same type
CCDC85B p.Arg96Leu Uncertain significance ★ ⚠ same type
CCDC85B p.Asn67Ser Uncertain significance ★ ⚠ same type
CCDC85B p.Asp201Asn Uncertain significance ★ ⚠ same type
CCDC85B p.Cys198Arg 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/ccdc85b-p-glu23asp (accessed [today's date]).

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