Is CFAP410 p.Ser166Phe (c.497C>T) pathogenic?

CFAP410 p.Ser166Phe (c.497C>T) is classified Uncertain significance in CFAP410 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-05). AlphaMissense: likely benign (0.1208); Very rare (popmax 0.000424%, nfe).

How common is CFAP410 p.Ser166Phe (c.497C>T) in the general population?

CFAP410 p.Ser166Phe (c.497C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about CFAP410 p.Ser166Phe (c.497C>T)?

AlphaMissense predicts likely benign (score 0.1208) — an in-silico prediction, not a clinical call.

CFAP410 p.Ser166Phe

c.497C>T · rs747351700 · VCV2101921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1208 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1208	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -8.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.2, phastCons 0.01
Regional constraint	o/e 1.21	unconstrained · MANE · 8,993 bp · p 8.7e-05 · regional, not allelic
Overall
CADD	20.3	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 0.000424% European (non-Finnish) · 5/1,179,816 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,612,910 alleles · very rare exomes 5/1,460,534 · genomes 0/152,376 · joint denominator

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.Ser166Phe
Coding: c.497C>T
MANE Select: NM_004928
dbSNP: rs747351700
Type: single nucleotide variant
Location: chr21:44331891 (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.Ser166= 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-ser166phe (accessed [today's date]).

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