Is CFAP46 p.Asn1707Ser (c.5120A>G) pathogenic?

CFAP46 p.Asn1707Ser (c.5120A>G) is classified Uncertain significance in CFAP46 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-22). AlphaMissense: likely benign (0.0703); Very rare (popmax 0.00548%, afr).

How common is CFAP46 p.Asn1707Ser (c.5120A>G) in the general population?

CFAP46 p.Asn1707Ser (c.5120A>G) is very rare (popmax 0.00548%, afr) (gnomAD).

What do computational predictors say about CFAP46 p.Asn1707Ser (c.5120A>G)?

AlphaMissense predicts likely benign (score 0.0703) — an in-silico prediction, not a clinical call.

CFAP46 p.Asn1707Ser

c.5120A>G · rs1277061464 · VCV2256550

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0703 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00548%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0703	likely benign
REVEL	0.002	strongly benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.26	GERP -3.9
Regional constraint	o/e 0.94	unconstrained · MANE · 134 kb · p 0.00093 · regional, not allelic
Overall
CADD	0.044	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 0.00548% African / African-American · 4/73,008 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.000451% 7/1,550,920 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00548%	18,252
Remaining individualsnot grpmax-eligible	0.00332%	30,124
European (non-Finnish)	8.72e-05%	1,147,036

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.Asn1707Ser
Coding: c.5120A>G
MANE Select: NM_001200049
dbSNP: rs1277061464
Type: single nucleotide variant
Location: chr10:132860495 (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-asn1707ser (accessed [today's date]).

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