Is CFAP100 p.Asp487Asn (c.1459G>A) pathogenic?

CFAP100 p.Asp487Asn (c.1459G>A) is classified Uncertain significance in CFAP100 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-27). AlphaMissense: likely benign (0.111); Very rare (popmax 0.00659%, sas).

How common is CFAP100 p.Asp487Asn (c.1459G>A) in the general population?

CFAP100 p.Asp487Asn (c.1459G>A) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about CFAP100 p.Asp487Asn (c.1459G>A)?

AlphaMissense predicts likely benign (score 0.111) — an in-silico prediction, not a clinical call.

CFAP100 p.Asp487Asn

c.1459G>A · VCV3491139

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.111 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.111	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -7.82	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 4.4	GERP -2.6, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 40 kb · p 0.22 · regional, not allelic
Overall
CADD	21.5	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 0.00659% South Asian · 6/91,040 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000411% 6/1,461,446 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: CFAP100
Protein: p.Asp487Asn
Coding: c.1459G>A
MANE Select: NM_182628
Type: single nucleotide variant
Location: chr3:126434212 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.85 · 1 PDB
Residue 487: the 'interaction with ttll13' region

Full CFAP100 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP100 p.Asp487Tyr Uncertain significance ★ ⚠ same residue
CFAP100 p.Ala126Ser Uncertain significance ★ ⚠ same type
CFAP100 p.Ala179Val Uncertain significance ★ ⚠ same type
CFAP100 p.Ala224Asp Uncertain significance ★ ⚠ same type
CFAP100 p.Ala499Thr Uncertain significance ★ ⚠ same type
CFAP100 p.Ala563Val Uncertain significance ★ ⚠ same type
CFAP100 p.Ala565Val Uncertain significance ★ ⚠ same type
CFAP100 p.Ala73Pro 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/cfap100-p-asp487asn (accessed [today's date]).

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