Is CFAP100 p.Ala565Val (c.1694C>T) pathogenic?

CFAP100 p.Ala565Val (c.1694C>T) is classified Uncertain significance in CFAP100 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-06-23). AlphaMissense: likely benign (0.1357); Ultra-rare (popmax 0.0227%, nfe).

How common is CFAP100 p.Ala565Val (c.1694C>T) in the general population?

CFAP100 p.Ala565Val (c.1694C>T) is ultra-rare (popmax 0.0227%, nfe) (gnomAD).

What do computational predictors say about CFAP100 p.Ala565Val (c.1694C>T)?

AlphaMissense predicts likely benign (score 0.1357) — an in-silico prediction, not a clinical call.

CFAP100 p.Ala565Val

c.1694C>T · rs373742550 · VCV2228355

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1357 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1357	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -7.17	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 2.6	GERP 1.8, phastCons 0.99
Regional constraint	o/e 1.04	unconstrained · MANE · 40 kb · p 0.22 · regional, not allelic
Overall
CADD	22.6	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 0.0227% European (non-Finnish) · 268/1,178,438 alleles

Filtering AF 0.0205% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0196%

Overall 0.0184% 296/1,611,572 alleles · ultra-rare exomes 278/1,459,612 · genomes 18/151,960 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0227%	4,397
African / African-American	0.0227%	4,401
Remaining individualsnot grpmax-eligible	0.0112%	8,906
East Asian	0.00447%	22,352
Admixed American	0.00334%	29,945

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.Ala565Val
Coding: c.1694C>T
MANE Select: NM_182628
dbSNP: rs373742550
Type: single nucleotide variant
Location: chr3:126435624 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.85 · 1 PDB
Residue 565: the 'interaction with ttll13' region

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.Ala73Pro 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-ala565val (accessed [today's date]).

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