Is CEP170B p.Ala441= (c.1323C>T) pathogenic?

CEP170B p.Ala441= (c.1323C>T) is classified Benign in CEP170B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-01). Common (popmax 5.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CEP170B-related disorder.

What condition is associated with CEP170B p.Ala441= (c.1323C>T)?

CEP170B p.Ala441= (c.1323C>T) is associated with CEP170B-related disorder (ClinVar).

CEP170B p.Ala441=

Q: How common is CEP170B p.Ala441= (c.1323C>T) in the general population?

CEP170B p.Ala441= (c.1323C>T) is common (popmax 5.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1323C>T · rs143836703 · VCV3055568

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 5.3%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

CEP170B-related disorder

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 -20	GERP -2.1
Overall
CADD	0.407	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.3% African / African-American · 3,937/74,340 alleles

Filtering AF 5.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.1%

Overall 0.278% 4,396/1,579,062 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.3%	19
Remaining individualsnot grpmax-eligible	0.345%	290
Admixed American	0.325%	308
Middle Eastern	0.166%	602
South Asian	0.0092%	10,872
European (non-Finnish)	0.00421%	23,735
Finnishnot grpmax-eligible	0.00336%	29,806
East Asian	0.00231%	43,226

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: CEP170B
Protein: p.Ala441=
Coding: c.1323C>T
MANE Select: NM_001112726
dbSNP: rs143836703
Type: single nucleotide variant
Location: chr14:104884102 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.31
Residue 441: the 'disordered' region

Full CEP170B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CEP170B-related disorder

Similar variants

CEP170B c.3879-7G>C Benign same condition
CEP170B c.3879-8G>A Benign same condition
CEP170B c.4271+8G>A Likely benign same condition
CEP170B c.4365+7G>A Likely benign same condition
CEP170B p.Ala1177= Likely benign same condition
CEP170B p.Ala127= Likely benign same condition
CEP170B p.Ala302Val Likely benign same condition
CEP170B p.Ala369Val Likely benign same condition

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/cep170b-p-ala441 (accessed [today's date]).

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