Is CFAP46 p.Arg484Ser (c.1450C>A) pathogenic?

CFAP46 p.Arg484Ser (c.1450C>A) is classified Likely benign in CFAP46 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: ambiguous (0.3912); Rare (popmax 0.659%, nfe).

How common is CFAP46 p.Arg484Ser (c.1450C>A) in the general population?

CFAP46 p.Arg484Ser (c.1450C>A) is rare (popmax 0.659%, nfe) (gnomAD).

What do computational predictors say about CFAP46 p.Arg484Ser (c.1450C>A)?

AlphaMissense predicts ambiguous (score 0.3912) — an in-silico prediction, not a clinical call.

CFAP46 p.Arg484Ser

c.1450C>A · rs41302993 · VCV2640995

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3912 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.659%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3912	ambiguous
REVEL	0.119	moderately benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 134 kb · p 0.00093 · regional, not allelic
Overall
CADD	16.86	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.659% European (non-Finnish) · 7,549/1,145,370 alleles

Filtering AF 0.647% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.641%

Overall 0.654% 10,114/1,545,324 alleles · rare exomes 9,152/1,392,988 · genomes 962/152,336 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.1%	32
European (non-Finnish)grpmax	0.659%	152
Remaining individualsnot grpmax-eligible	0.511%	196
South Asian	0.32%	312
Admixed American	0.298%	335
Ashkenazi Jewishnot grpmax-eligible	0.133%	753
African / African-American	0.0752%	1,329
Middle Eastern	0.0186%	5,362
East Asian	0.00245%	40,842

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CFAP46
Protein: p.Arg484Ser
Coding: c.1450C>A
MANE Select: NM_001200049
dbSNP: rs41302993
Type: single nucleotide variant
Location: chr10:132922515 (GRCh38)
Gene constraint: LOEUF 0.888 · pLI <0.01 (gnomAD)

Full CFAP46 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP46 p.Ala1708Val Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1742Glu Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1742Val Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1746Glu Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1788Val Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1806Val Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1811Val Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1871Val 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/cfap46-p-arg484ser (accessed [today's date]).

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