Is CFAP298 p.Lys76Arg (c.227A>G) pathogenic?

CFAP298 p.Lys76Arg (c.227A>G) is classified Uncertain significance in CFAP298 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-30). AlphaMissense: likely benign (0.0629); Ultra-rare (popmax 0.078%, sas).

How common is CFAP298 p.Lys76Arg (c.227A>G) in the general population?

CFAP298 p.Lys76Arg (c.227A>G) is ultra-rare (popmax 0.078%, sas) (gnomAD).

What do computational predictors say about CFAP298 p.Lys76Arg (c.227A>G)?

AlphaMissense predicts likely benign (score 0.0629) — an in-silico prediction, not a clinical call.

CFAP298 p.Lys76Arg

c.227A>G · rs568749302 · VCV2077659

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0629 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.078%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0629	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -8.20	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -1.6, phastCons 0.019
Regional constraint	o/e 0.97	unconstrained · MANE · 10 kb · p 0.52 · regional, not allelic
Overall
CADD	15.03	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 0.078% South Asian · 71/91,072 alleles

Filtering AF 0.0633% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.058%

Overall 0.00781% 126/1,614,176 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.078%	1,283
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0064%	15,626
European (non-Finnish)	0.00398%	25,106
Admixed American	0.00333%	30,017
African / African-American	0.00133%	75,072

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: CFAP298
Protein: p.Lys76Arg
Coding: c.227A>G
MANE Select: NM_021254
dbSNP: rs568749302
Type: single nucleotide variant
Location: chr21:32609918 (GRCh38)
Gene constraint: LOEUF 1.267 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54

Full CFAP298 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP298 p.Arg98Ter Pathogenic/Likely pathogenic ★★ same type
CFAP298 p.Gln225Ter Pathogenic ★★ same type
CFAP298 p.Asp141Gly Uncertain significance ★★ ⚠ same type
CFAP298 p.Gln225Arg Uncertain significance ★★ ⚠ same type
CFAP298 p.Gly80Ser Uncertain significance ★★ ⚠ same type
CFAP298 c.308-16C>G Benign ★★ same type
CFAP298 c.375+15A>G Likely benign ★★ same type
CFAP298 c.376-20C>T Benign ★★ 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/cfap298-p-lys76arg (accessed [today's date]).

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