Is CFAP97 p.Ser378Phe (c.1133C>T) pathogenic?

CFAP97 p.Ser378Phe (c.1133C>T) is classified Uncertain significance in CFAP97 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely pathogenic (0.9524); Very rare (popmax 0.00424%, nfe).

How common is CFAP97 p.Ser378Phe (c.1133C>T) in the general population?

CFAP97 p.Ser378Phe (c.1133C>T) is very rare (popmax 0.00424%, nfe) (gnomAD).

What do computational predictors say about CFAP97 p.Ser378Phe (c.1133C>T)?

AlphaMissense predicts likely pathogenic (score 0.9524) — an in-silico prediction, not a clinical call.

CFAP97 p.Ser378Phe

c.1133C>T · VCV4001691

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9524 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00424%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9524	likely pathogenic · top 4% in CFAP97
REVEL	0.417	indeterminate
SaProt	LLR -12.48	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 28 kb · p 0.14 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00424% European (non-Finnish) · 50/1,179,856 alleles

Filtering AF 0.00326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00294%

Overall 0.0031% 50/1,613,594 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: CFAP97
Protein: p.Ser378Phe
Coding: c.1133C>T
MANE Select: NM_020827
Type: single nucleotide variant
Location: chr4:185175973 (GRCh38)
Gene constraint: LOEUF 1.095 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.55

Full CFAP97 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP97 p.Glu383= Benign ★★ same type
CFAP97 p.Thr499Met Benign ★★ same type
CFAP97 p.Ala152Gly Uncertain significance ★ ⚠ same type
CFAP97 p.Ala448Thr Uncertain significance ★ ⚠ same type
CFAP97 p.Arg381Ser Uncertain significance ★ ⚠ same type
CFAP97 p.Arg389Gln Uncertain significance ★ ⚠ same type
CFAP97 p.Arg457His Uncertain significance ★ ⚠ same type
CFAP97 p.Arg479Trp 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/cfap97-p-ser378phe (accessed [today's date]).

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