Is CEP170B p.Ala1306Val (c.3917C>T) pathogenic?

CEP170B p.Ala1306Val (c.3917C>T) is classified Uncertain significance in CEP170B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). Very rare (popmax 6.99e-05%).

How common is CEP170B p.Ala1306Val (c.3917C>T) in the general population?

CEP170B p.Ala1306Val (c.3917C>T) is very rare (popmax 6.99e-05%) (gnomAD).

CEP170B p.Ala1306Val

c.3917C>T · VCV4000775

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.99e-05%)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.455	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 19 kb · p 0.99 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.99e-05%

Overall 6.99e-05% 1/1,430,180 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: CEP170B
Protein: p.Ala1306Val
Coding: c.3917C>T
MANE Select: NM_001112726
Type: single nucleotide variant
Location: chr14:104893014 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.31
Residue 1306: the 'disordered' region

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

Similar variants

CEP170B p.Lys368Glu Uncertain significance ★★ same type
CEP170B p.Pro148Leu Uncertain significance ★★ same type
CEP170B p.Ala259Val Benign ★★ same type
CEP170B p.Arg147= Benign ★★ same type
CEP170B p.Ala1053Val Uncertain significance ★ same type
CEP170B p.Ala1062Val Uncertain significance ★ same type
CEP170B p.Ala1083Val Uncertain significance ★ same type
CEP170B p.Ala1091Thr 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/cep170b-p-ala1306val (accessed [today's date]).

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