Is CCDC85A p.Ser2Trp (c.5C>G) pathogenic?

CCDC85A p.Ser2Trp (c.5C>G) is classified Uncertain significance in CCDC85A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-14). AlphaMissense: likely pathogenic (0.7264); Ultra-rare (popmax 0.0104%, nfe).

How common is CCDC85A p.Ser2Trp (c.5C>G) in the general population?

CCDC85A p.Ser2Trp (c.5C>G) is ultra-rare (popmax 0.0104%, nfe) (gnomAD).

What do computational predictors say about CCDC85A p.Ser2Trp (c.5C>G)?

AlphaMissense predicts likely pathogenic (score 0.7264) — an in-silico prediction, not a clinical call.

CCDC85A p.Ser2Trp

c.5C>G · rs917672547 · VCV3139469

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7264 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0104%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7264	likely pathogenic
REVEL	0.216	benign-leaning
SaProt	LLR -10.01	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 0.99, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 200 kb · p 0.0042 · regional, not allelic
Overall
CADD	24.7	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 0.0104% European (non-Finnish) · 115/1,104,434 alleles

Filtering AF 0.00882% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00827%

Overall 0.00806% 115/1,426,370 alleles · ultra-rare exomes 112/1,274,384 · genomes 3/151,986 · joint denominator

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: CCDC85A
Protein: p.Ser2Trp
Coding: c.5C>G
MANE Select: NM_001080433
dbSNP: rs917672547
Type: single nucleotide variant
Location: chr2:56184629 (GRCh38)
Gene constraint: LOEUF 1.058 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.16
Residue 2: the 'disordered' region

Full CCDC85A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC85A p.Ala13Val Uncertain significance ★ ⚠ same type
CCDC85A p.Ala142Ser Uncertain significance ★ ⚠ same type
CCDC85A p.Ala178Val Uncertain significance ★ ⚠ same type
CCDC85A p.Ala201Pro Uncertain significance ★ ⚠ same type
CCDC85A p.Ala201Val Uncertain significance ★ ⚠ same type
CCDC85A p.Ala21Ser Uncertain significance ★ ⚠ same type
CCDC85A p.Ala21Val Uncertain significance ★ ⚠ same type
CCDC85A p.Ala28Asp 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/ccdc85a-p-ser2trp (accessed [today's date]).

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