Is CFAP410 p.Leu92= (c.276G>A) pathogenic?

CFAP410 p.Leu92= (c.276G>A) is classified Likely benign in CFAP410 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-01). Ultra-rare (popmax 0.0118%, nfe).

How common is CFAP410 p.Leu92= (c.276G>A) in the general population?

CFAP410 p.Leu92= (c.276G>A) is ultra-rare (popmax 0.0118%, nfe) (gnomAD).

CFAP410 p.Leu92=

c.276G>A · rs374507502 · VCV1085912

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0118%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.45	GERP -0.99, phastCons 0.031
Overall
CADD	6.052	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0118% European (non-Finnish) · 139/1,179,642 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00956%

Overall 0.0101% 162/1,611,854 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0128%	7,790
European (non-Finnish)grpmax	0.0118%	8,487
Admixed American	0.0117%	8,566
South Asian	0.00659%	15,167
East Asian	0.00223%	44,862
African / African-American	0.00133%	74,930

Remaining individuals 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: CFAP410
Protein: p.Leu92=
Coding: c.276G>A
MANE Select: NM_004928
dbSNP: rs374507502
Type: single nucleotide variant
Location: chr21:44333130 (GRCh38)
Gene constraint: LOEUF 1.453 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.77 · 1 PDB

Full CFAP410 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP410 c.545+1G>A Pathogenic ★★ same type
CFAP410 c.642+2T>C Pathogenic ★★ same type
CFAP410 c.643-1G>C Pathogenic ★★ same type
CFAP410 c.643-23A>T Pathogenic/Likely pathogenic ★★ same type
CFAP410 c.96+1G>A Pathogenic ★★ same type
CFAP410 c.96+1G>T Pathogenic/Likely pathogenic ★★ same type
CFAP410 p.Arg73Pro Pathogenic/Likely pathogenic ★★ ⚠ same type
CFAP410 p.Gln119Ter Pathogenic ★★ 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/cfap410-p-leu92 (accessed [today's date]).

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