Is CFAP100 p.Arg334Trp (c.1000C>T) pathogenic?

CFAP100 p.Arg334Trp (c.1000C>T) is classified Uncertain significance in CFAP100 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-24). AlphaMissense: likely benign (0.1057); Rare (popmax 0.168%, mid).

How common is CFAP100 p.Arg334Trp (c.1000C>T) in the general population?

CFAP100 p.Arg334Trp (c.1000C>T) is rare (popmax 0.168%, mid) (gnomAD).

What do computational predictors say about CFAP100 p.Arg334Trp (c.1000C>T)?

AlphaMissense predicts likely benign (score 0.1057) — an in-silico prediction, not a clinical call.

CFAP100 p.Arg334Trp

c.1000C>T · rs781053138 · VCV2460871

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1057 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.168%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1057	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -8.06	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 0.008	GERP -1.3
Regional constraint	o/e 1.04	unconstrained · MANE · 40 kb · p 0.22 · regional, not allelic
Overall
CADD	17.41	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 0.168% Middle Eastern · 10/5,960 alleles

Filtering AF 0.091% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0693%

Overall 0.0075% 121/1,612,646 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.168%	596
South Asian	0.0417%	2,397
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,932
Remaining individualsnot grpmax-eligible	0.0176%	5,671
African / African-American	0.00534%	18,736
European (non-Finnish)	0.00424%	23,599
Admixed American	0.00333%	29,998

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.Arg334Trp
Coding: c.1000C>T
MANE Select: NM_182628
dbSNP: rs781053138
Type: single nucleotide variant
Location: chr3:126420147 (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.Arg334Gly Uncertain significance ★ ⚠ same residue
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.Ala73Pro 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-arg334trp (accessed [today's date]).

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