Is CFAP46 p.Tyr1269= (c.3807C>T) pathogenic?

CFAP46 p.Tyr1269= (c.3807C>T) is classified Likely benign in CFAP46 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). Very rare (popmax 0.00496%, sas).

How common is CFAP46 p.Tyr1269= (c.3807C>T) in the general population?

CFAP46 p.Tyr1269= (c.3807C>T) is very rare (popmax 0.00496%, sas) (gnomAD).

CFAP46 p.Tyr1269=

c.3807C>T · rs1223254205 · VCV2640988

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00496%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.75	GERP -3.3
Overall
CADD	1.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00496% South Asian · 4/80,614 alleles

Filtering AF 0.00166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.0019% 29/1,527,454 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00496%	20,153
East Asian	0.00493%	20,296
European (non-Finnish)	0.00194%	51,677
Remaining individualsnot grpmax-eligible	0.0017%	58,980

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.Tyr1269=
Coding: c.3807C>T
MANE Select: NM_001200049
dbSNP: rs1223254205
Type: single nucleotide variant
Location: chr10:132879624 (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-tyr1269 (accessed [today's date]).

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