Is CFAP100 p.Ala73Pro (c.217G>C) pathogenic?

CFAP100 p.Ala73Pro (c.217G>C) is classified Uncertain significance in CFAP100 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-23). AlphaMissense: ambiguous (0.5477); Very rare (popmax 0.00439%, sas).

How common is CFAP100 p.Ala73Pro (c.217G>C) in the general population?

CFAP100 p.Ala73Pro (c.217G>C) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about CFAP100 p.Ala73Pro (c.217G>C)?

AlphaMissense predicts ambiguous (score 0.5477) — an in-silico prediction, not a clinical call.

CFAP100 p.Ala73Pro

c.217G>C · VCV3832226

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5477 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5477	ambiguous
REVEL	0.017	moderately benign-leaning
SaProt	LLR -13.59	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 -0.062	GERP -3.7, phastCons 0.001
Regional constraint	o/e 1.04	unconstrained · MANE · 40 kb · p 0.22 · regional, not allelic
Overall
CADD	13.62	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 0.00439% South Asian · 4/91,044 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000372% 6/1,612,728 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,761
Remaining individualsnot grpmax-eligible	0.0016%	62,450
European (non-Finnish)	8.48e-05%	1,178,862

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: CFAP100
Protein: p.Ala73Pro
Coding: c.217G>C
MANE Select: NM_182628
Type: single nucleotide variant
Location: chr3:126414171 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.85 · 1 PDB

Full CFAP100 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP100 p.Ala126Ser Uncertain significance ★ ⚠ same type
CFAP100 p.Ala179Val Uncertain significance ★ ⚠ same type
CFAP100 p.Ala224Asp Uncertain significance ★ ⚠ same type
CFAP100 p.Ala499Thr Uncertain significance ★ ⚠ same type
CFAP100 p.Ala563Val Uncertain significance ★ ⚠ same type
CFAP100 p.Ala565Val Uncertain significance ★ ⚠ same type
CFAP100 p.Arg103Gln Uncertain significance ★ ⚠ same type
CFAP100 p.Arg103Trp 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/cfap100-p-ala73pro (accessed [today's date]).

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