Is CEP126 p.Phe370Ser (c.1109T>C) pathogenic?

CEP126 p.Phe370Ser (c.1109T>C) is classified Uncertain significance in CEP126 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). AlphaMissense: likely benign (0.0882); Ultra-rare (popmax 0.0284%, amr).

How common is CEP126 p.Phe370Ser (c.1109T>C) in the general population?

CEP126 p.Phe370Ser (c.1109T>C) is ultra-rare (popmax 0.0284%, amr) (gnomAD).

What do computational predictors say about CEP126 p.Phe370Ser (c.1109T>C)?

AlphaMissense predicts likely benign (score 0.0882) — an in-silico prediction, not a clinical call.

CEP126 p.Phe370Ser

c.1109T>C · VCV3490476

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0882 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0284%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0882	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -4.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.67, phastCons 0.061
Regional constraint	o/e 0.99	unconstrained · MANE · 67 kb · p 0.63 · regional, not allelic
Overall
CADD	8.041	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0284% Admixed American · 17/59,842 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0148%

Overall 0.00123% 18/1,460,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0284%	3,520
Remaining individualsnot grpmax-eligible	0.0016%	62,446

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: CEP126
Protein: p.Phe370Ser
Coding: c.1109T>C
MANE Select: NM_020802
Type: single nucleotide variant
Location: chr11:101962144 (GRCh38)
Gene constraint: LOEUF 0.732 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.44

Full CEP126 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP126 p.Gln146Glu Benign ★★ same type
CEP126 p.His308Leu Benign ★★ same type
CEP126 p.Leu226= Benign ★★ same type
CEP126 p.Met1021Thr Benign ★★ same type
CEP126 p.Pro710Ser Benign ★★ same type
CEP126 p.Ser372Pro Benign ★★ same type
CEP126 p.Ala1028Thr Uncertain significance ★ ⚠ same type
CEP126 p.Ala460Val 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/cep126-p-phe370ser (accessed [today's date]).

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