Is CFAP119 p.Arg181Trp (c.541C>T) pathogenic?

CFAP119 p.Arg181Trp (c.541C>T) is classified Uncertain significance in CFAP119 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: ambiguous (0.3879); Very rare (popmax 0.00446%, eas).

How common is CFAP119 p.Arg181Trp (c.541C>T) in the general population?

CFAP119 p.Arg181Trp (c.541C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CFAP119 p.Arg181Trp (c.541C>T)?

AlphaMissense predicts ambiguous (score 0.3879) — an in-silico prediction, not a clinical call.

CFAP119 p.Arg181Trp

c.541C>T · rs1489597128 · VCV3143306

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Computational evidence

Protein change
AlphaMissense	0.3879	ambiguous
REVEL	0.324	indeterminate
SaProt	LLR -14.85	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 2.3, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 4,269 bp · p 0.72 · regional, not allelic
Overall
CADD	32.0	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 0.00446% East Asian · 2/44,892 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.00041% 6/1,461,882 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,446
South Asian	0.0011%	91,082
European (non-Finnish)	0.000254%	393,346

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: CFAP119
Protein: p.Arg181Trp
Coding: c.541C>T
MANE Select: NM_001014979
dbSNP: rs1489597128
Type: single nucleotide variant
Location: chr16:30759458 (GRCh38)
Structure: AlphaFold pLDDT 74.17

Full CFAP119 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP119 p.Ala118Thr Uncertain significance ★ ⚠ same type
CFAP119 p.Ala127Thr Uncertain significance ★ ⚠ same type
CFAP119 p.Ala143Val Uncertain significance ★ ⚠ same type
CFAP119 p.Ala196Ser Uncertain significance ★ ⚠ same type
CFAP119 p.Ala196Val Uncertain significance ★ ⚠ same type
CFAP119 p.Ala53Val Uncertain significance ★ ⚠ same type
CFAP119 p.Arg132Cys Uncertain significance ★ ⚠ same type
CFAP119 p.Arg207His 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/cfap119-p-arg181trp (accessed [today's date]).

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