Is CFAP44 p.Arg522Gln (c.1565G>A) pathogenic?

CFAP44 p.Arg522Gln (c.1565G>A) is classified Uncertain significance in CFAP44 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-25). AlphaMissense: likely benign (0.0701); Ultra-rare (popmax 0.0355%, afr); Associated with Inborn genetic diseases.

What condition is associated with CFAP44 p.Arg522Gln (c.1565G>A)?

CFAP44 p.Arg522Gln (c.1565G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CFAP44 p.Arg522Gln (c.1565G>A) in the general population?

CFAP44 p.Arg522Gln (c.1565G>A) is ultra-rare (popmax 0.0355%, afr) (gnomAD).

What do computational predictors say about CFAP44 p.Arg522Gln (c.1565G>A)?

AlphaMissense predicts likely benign (score 0.0701) — an in-silico prediction, not a clinical call.

CFAP44 p.Arg522Gln

c.1565G>A · rs558551986 · VCV3143481

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0701 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0355%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0701	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.75	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 -11	GERP -4.8
Regional constraint	o/e 0.93	unconstrained · MANE · 129 kb · p 0.0018 · regional, not allelic
Overall
CADD	0.018	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 0.0355% African / African-American · 26/73,256 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0213%

Overall 0.00438% 69/1,575,384 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0355%	2,818
Ashkenazi Jewishnot grpmax-eligible	0.0282%	3,547
Remaining individualsnot grpmax-eligible	0.00494%	20,224
East Asian	0.00457%	21,862
South Asian	0.00243%	41,073
European (non-Finnish)	0.00223%	44,800
Admixed American	0.00191%	52,414
Finnishnot grpmax-eligible	0.00158%	63,176

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: CFAP44
Protein: p.Arg522Gln
Coding: c.1565G>A
MANE Select: NM_001164496
dbSNP: rs558551986
Type: single nucleotide variant
Location: chr3:113399910 (GRCh38)
Gene constraint: LOEUF 0.697 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.87 · 1 PDB
Residue 522: a UniProt-annotated variant site (in spgf20)

Full CFAP44 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP44 p.Ala161Gly Uncertain significance ★ ⚠ same condition
CFAP44 p.Ala712Val Uncertain significance ★ ⚠ same condition
CFAP44 p.Arg495Gln Uncertain significance ★ ⚠ same condition
CFAP44 p.Arg557Gln Uncertain significance ★ ⚠ same condition
CFAP44 p.Arg585Cys Uncertain significance ★ ⚠ same condition
CFAP44 p.Arg606Met Uncertain significance ★ ⚠ same condition
CFAP44 p.Arg703Met Uncertain significance ★ ⚠ same condition
CFAP44 p.Arg799His Conflicting classifications of pathogenicity ★ ⚠ same condition

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/cfap44-p-arg522gln (accessed [today's date]).

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