Is CEP85 p.Ala176= (c.528G>A) pathogenic?

CEP85 p.Ala176= (c.528G>A) is classified Benign in CEP85 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-26). Common (popmax 6.52%, afr) — too common for a highly-penetrant pathogenic allele.

CEP85 p.Ala176=

Q: How common is CEP85 p.Ala176= (c.528G>A) in the general population?

CEP85 p.Ala176= (c.528G>A) is common (popmax 6.52%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.528G>A · rs34867486 · VCV790484

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.52%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.75, phastCons 0.99
Overall
CADD	8.015	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.52% African / African-American · 4,889/74,988 alleles

Filtering AF 6.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.3%

Overall 0.368% 5,944/1,614,070 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.52%	15
Admixed American	0.64%	156
Middle Eastern	0.578%	173
Remaining individualsnot grpmax-eligible	0.549%	182
South Asian	0.0253%	3,960
East Asian	0.0245%	4,081
European (non-Finnish)	0.0219%	4,574
Finnishnot grpmax-eligible	0.00156%	64,010

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: CEP85
Protein: p.Ala176=
Coding: c.528G>A
MANE Select: NM_001319944
dbSNP: rs34867486
Type: single nucleotide variant
Location: chr1:26255490 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.09 · 2 PDB

Full CEP85 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP85 p.Ala176Val Likely benign ★ same residue
CEP85 p.Leu405Phe Benign ★★ same type
CEP85 p.Ala374Pro Uncertain significance ★ ⚠ same type
CEP85 p.Ala396Thr Uncertain significance ★ ⚠ same type
CEP85 p.Ala399Ser Uncertain significance ★ ⚠ same type
CEP85 p.Ala656Val Uncertain significance ★ ⚠ same type
CEP85 p.Arg146Lys Uncertain significance ★ ⚠ same type
CEP85 p.Arg177Lys 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/cep85-p-ala176 (accessed [today's date]).

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