Is CCDC85A p.Gly485Arg (c.1453G>C) pathogenic?

CCDC85A p.Gly485Arg (c.1453G>C) is classified Uncertain significance in CCDC85A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: ambiguous (0.4348); Very rare (popmax 0.000339%, nfe).

How common is CCDC85A p.Gly485Arg (c.1453G>C) in the general population?

CCDC85A p.Gly485Arg (c.1453G>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about CCDC85A p.Gly485Arg (c.1453G>C)?

AlphaMissense predicts ambiguous (score 0.4348) — an in-silico prediction, not a clinical call.

CCDC85A p.Gly485Arg

c.1453G>C · rs780223971 · VCV2484813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4348 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4348	ambiguous
REVEL	0.14	moderately benign-leaning
SaProt	LLR -5.77	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Pangolin	Δ0.32	gain · loss 0.25 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 9.7	GERP 2.1, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 200 kb · p 0.0042 · regional, not allelic
Overall
CADD	29.9	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 0.000339% European (non-Finnish) · 4/1,179,610 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,124 alleles · very rare exomes 4/1,460,888 · genomes 0/152,236 · 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.Gly485Arg
Coding: c.1453G>C
MANE Select: NM_001080433
dbSNP: rs780223971
Type: single nucleotide variant
Location: chr2:56375816 (GRCh38)
Gene constraint: LOEUF 1.058 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.16

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

Similar variants

CCDC85A p.Gly485Cys Uncertain significance ★ ⚠ same residue
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

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-gly485arg (accessed [today's date]).

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