Is CFAP410 p.Pro40Leu (c.119C>T) pathogenic?

CFAP410 p.Pro40Leu (c.119C>T) is classified Uncertain significance in CFAP410 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-05). AlphaMissense: ambiguous (0.4771); Very rare (popmax 0.00967%, nfe).

How common is CFAP410 p.Pro40Leu (c.119C>T) in the general population?

CFAP410 p.Pro40Leu (c.119C>T) is very rare (popmax 0.00967%, nfe) (gnomAD).

What do computational predictors say about CFAP410 p.Pro40Leu (c.119C>T)?

AlphaMissense predicts ambiguous (score 0.4771) — an in-silico prediction, not a clinical call.

CFAP410 p.Pro40Leu

c.119C>T · rs750561784 · VCV1018518

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4771 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00967%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4771	ambiguous
REVEL	0.259	benign-leaning
SaProt	LLR -11.29	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	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	25.6	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 0.00967% European (non-Finnish) · 113/1,168,494 alleles

Filtering AF 0.00817% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00767%

Overall 0.00729% 116/1,592,188 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00967%	10,341
Remaining individualsnot grpmax-eligible	0.00487%	20,543

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.Pro40Leu
Coding: c.119C>T
MANE Select: NM_004928
dbSNP: rs750561784
Type: single nucleotide variant
Location: chr21:44335782 (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 p.Pro40= Likely benign ★ 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
CFAP410 p.Arg73Pro 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-pro40leu (accessed [today's date]).

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