Is CFAP44 p.Pro740Thr (c.2218C>A) pathogenic?

CFAP44 p.Pro740Thr (c.2218C>A) is classified Uncertain significance in CFAP44 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.2524); Very rare (popmax 0.0055%, sas); Associated with Inborn genetic diseases.

What condition is associated with CFAP44 p.Pro740Thr (c.2218C>A)?

CFAP44 p.Pro740Thr (c.2218C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CFAP44 p.Pro740Thr (c.2218C>A) in the general population?

CFAP44 p.Pro740Thr (c.2218C>A) is very rare (popmax 0.0055%, sas) (gnomAD).

What do computational predictors say about CFAP44 p.Pro740Thr (c.2218C>A)?

AlphaMissense predicts likely benign (score 0.2524) — an in-silico prediction, not a clinical call.

CFAP44 p.Pro740Thr

c.2218C>A · VCV4226981

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2524 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0055%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2524	likely benign
REVEL	0.313	indeterminate
SaProt	LLR -10.93	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 129 kb · p 0.0018 · regional, not allelic
Overall
CADD	23.6	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 0.0055% South Asian · 5/90,880 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.00136% 22/1,612,696 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0055%	18,176
Remaining individualsnot grpmax-eligible	0.0016%	62,428
European (non-Finnish)	0.00136%	73,708

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.Pro740Thr
Coding: c.2218C>A
MANE Select: NM_001164496
Type: single nucleotide variant
Location: chr3:113379386 (GRCh38)
Gene constraint: LOEUF 0.697 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.87 · 1 PDB
Residue 740: the 'disordered' region; 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.Pro740Ala Uncertain significance ★ ⚠ same residue
CFAP44 p.Ala161Gly Uncertain significance ★ ⚠ same condition
CFAP44 p.Ala712Val Uncertain significance ★ ⚠ same condition
CFAP44 p.Arg495Gln Uncertain significance ★ ⚠ same condition
CFAP44 p.Arg522Gln 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

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-pro740thr (accessed [today's date]).

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