Is CFAP44 p.Pro4Leu (c.11C>T) pathogenic?

CFAP44 p.Pro4Leu (c.11C>T) is classified Uncertain significance in CFAP44 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: likely benign (0.1121); Ultra-rare (popmax 0.0567%, amr); Associated with Inborn genetic diseases.

What condition is associated with CFAP44 p.Pro4Leu (c.11C>T)?

CFAP44 p.Pro4Leu (c.11C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CFAP44 p.Pro4Leu (c.11C>T) in the general population?

CFAP44 p.Pro4Leu (c.11C>T) is ultra-rare (popmax 0.0567%, amr) (gnomAD).

What do computational predictors say about CFAP44 p.Pro4Leu (c.11C>T)?

AlphaMissense predicts likely benign (score 0.1121) — an in-silico prediction, not a clinical call.

CFAP44 p.Pro4Leu

c.11C>T · rs752885039 · VCV3143476

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1121 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0567%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1121	likely benign
REVEL	0.193	benign-leaning
SaProt	LLR -5.49	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 8.8	GERP 2, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 7,513 bp · p 0.55 · regional, not allelic
Overall
CADD	26.2	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 0.0567% Admixed American · 34/59,960 alleles

Filtering AF 0.0417% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0365%

Overall 0.00496% 80/1,612,500 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0567%	1,764
Remaining individualsnot grpmax-eligible	0.00801%	12,489
European (non-Finnish)	0.00348%	28,771

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.Pro4Leu
Coding: c.11C>T
MANE Select: NM_001164496
dbSNP: rs752885039
Type: single nucleotide variant
Location: chr3:113433654 (GRCh38)
Gene constraint: LOEUF 0.697 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.87 · 1 PDB
Residue 4: the 'disordered' region

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.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
CFAP44 p.Arg703Met 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-pro4leu (accessed [today's date]).

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