Is CFAP410 p.Leu135Pro (c.404T>C) pathogenic?

CFAP410 p.Leu135Pro (c.404T>C) is classified Uncertain significance in CFAP410 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-07). AlphaMissense: likely pathogenic (0.5906); Very rare (popmax 0.000679%, nfe).

How common is CFAP410 p.Leu135Pro (c.404T>C) in the general population?

CFAP410 p.Leu135Pro (c.404T>C) is very rare (popmax 0.000679%, nfe) (gnomAD).

What do computational predictors say about CFAP410 p.Leu135Pro (c.404T>C)?

AlphaMissense predicts likely pathogenic (score 0.5906) — an in-silico prediction, not a clinical call.

CFAP410 p.Leu135Pro

c.404T>C · rs1402134765 · VCV1946540

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5906 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000679%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5906	likely pathogenic
REVEL	0.261	benign-leaning
SaProt	LLR -10.90	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 8,993 bp · p 8.7e-05 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000679% European (non-Finnish) · 8/1,178,546 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000497% 8/1,610,566 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: CFAP410
Protein: p.Leu135Pro
Coding: c.404T>C
MANE Select: NM_004928
dbSNP: rs1402134765
Type: single nucleotide variant
Location: chr21:44331984 (GRCh38)
Gene constraint: LOEUF 1.453 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.77 · 1 PDB
Residue 135: the lrrct domain; the 'disordered' region

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

Similar variants

CFAP410 p.Leu135= Likely benign ★ same residue
CFAP410 p.Leu135fs Pathogenic ★ same residue
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

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-leu135pro (accessed [today's date]).

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