Is CFAP276 p.Lys28Ile (c.83A>T) pathogenic?

CFAP276 p.Lys28Ile (c.83A>T) is classified Uncertain significance in CFAP276 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely benign (0.1111); Absent from gnomAD v4.1.

How common is CFAP276 p.Lys28Ile (c.83A>T) in the general population?

CFAP276 p.Lys28Ile (c.83A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFAP276 p.Lys28Ile (c.83A>T)?

AlphaMissense predicts likely benign (score 0.1111) — an in-silico prediction, not a clinical call.

CFAP276 p.Lys28Ile

c.83A>T · rs1553246861 · VCV1264319

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1111 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1111	likely benign
REVEL	0.421	indeterminate
SaProt	LLR -5.94	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -0.95, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 6,648 bp · p 0.25 · regional, not allelic
Overall
CADD	23.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFAP276
Protein: p.Lys28Ile
Coding: c.83A>T
MANE Select: NM_001245025
dbSNP: rs1553246861
Type: single nucleotide variant
Location: chr1:109108036 (GRCh38)
Structure: AlphaFold pLDDT 67.55 · 2 PDB
Residue 28: the 'disordered' region; a UniProt-annotated variant site (found in patients with an intermediate form of charcot-marie-tooth disease; does not affect subcellular location; reduced protein expression; increased intracellular ca(2+))

Full CFAP276 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP276 p.Arg10Ser Uncertain significance ★ same type
CFAP276 p.Arg160Ter Uncertain significance ★ same type
CFAP276 p.Arg46Gln Uncertain significance ★ ⚠ same type
CFAP276 p.Gln143Glu Uncertain significance ★ ⚠ same type
CFAP276 c.45+725G>T Likely benign ★ same type
CFAP276 p.Ile122Asn 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/cfap276-p-lys28ile (accessed [today's date]).

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