Is CFAP221 p.Arg516Gln (c.1547G>A) pathogenic?

CFAP221 p.Arg516Gln (c.1547G>A) is classified Likely benign in CFAP221 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-01-05). AlphaMissense: likely benign (0.0773); Rare (popmax 0.265%, amr); Associated with CFAP221-related disorder.

What condition is associated with CFAP221 p.Arg516Gln (c.1547G>A)?

CFAP221 p.Arg516Gln (c.1547G>A) is associated with CFAP221-related disorder (ClinVar).

How common is CFAP221 p.Arg516Gln (c.1547G>A) in the general population?

CFAP221 p.Arg516Gln (c.1547G>A) is rare (popmax 0.265%, amr) (gnomAD).

What do computational predictors say about CFAP221 p.Arg516Gln (c.1547G>A)?

AlphaMissense predicts likely benign (score 0.0773) — an in-silico prediction, not a clinical call.

CFAP221 p.Arg516Gln

c.1547G>A · rs544476023 · VCV3033645

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0773 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.265%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CFAP221-related disorder

Computational evidence

Protein change
AlphaMissense	0.0773	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -6.16	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 -3.4	GERP -3.4
Regional constraint	o/e 1.01	unconstrained · MANE · 110 kb · p 0.72 · regional, not allelic
Overall
CADD	0.157	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 0.265% Admixed American · 159/59,958 alleles

Filtering AF 0.232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.219%

Overall 0.0148% 238/1,613,266 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.265%	377
South Asian	0.0638%	1,569
Remaining individualsnot grpmax-eligible	0.0064%	15,622
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,592
East Asian	0.00223%	44,856
European (non-Finnish)	0.00127%	78,649

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: CFAP221
Protein: p.Arg516Gln
Coding: c.1547G>A
MANE Select: NM_001271049
dbSNP: rs544476023
Type: single nucleotide variant
Location: chr2:119627683 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.53

Full CFAP221 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CFAP221-related disorder

Similar variants

CFAP221 c.1134-10_1134-9dup Likely benign same condition
CFAP221 p.Arg131Ter Pathogenic ★ same type
CFAP221 c.1025-1G>A Uncertain significance ★ same type
CFAP221 p.Asn834Asp Uncertain significance ★ same type
CFAP221 p.Ile567Asn Uncertain significance ★ ⚠ same type
CFAP221 p.Leu833Phe Uncertain significance ★ ⚠ same type
CFAP221 c.1311+7A>G Likely benign ★ same type
CFAP221 c.632-7C>G Likely 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/cfap221-p-arg516gln (accessed [today's date]).

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