Is CFAP44 p.Trp1441Cys (c.4323G>T) pathogenic?

CFAP44 p.Trp1441Cys (c.4323G>T) is classified Benign in CFAP44 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: ambiguous (0.5188); Ultra-rare (popmax 0.0174%, mid).

How common is CFAP44 p.Trp1441Cys (c.4323G>T) in the general population?

CFAP44 p.Trp1441Cys (c.4323G>T) is ultra-rare (popmax 0.0174%, mid) (gnomAD).

What do computational predictors say about CFAP44 p.Trp1441Cys (c.4323G>T)?

AlphaMissense predicts ambiguous (score 0.5188) — an in-silico prediction, not a clinical call.

CFAP44 p.Trp1441Cys

c.4323G>T · rs200617587 · VCV746970

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5188 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5188	ambiguous
REVEL	0.09	moderately benign-leaning
SaProt	LLR -6.37	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.3, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 129 kb · p 0.0018 · regional, not allelic
Overall
CADD	22.8	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 0.0174% Middle Eastern · 1/5,758 alleles

Filtering AF 0.0131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0123%

Overall 0.0659% 970/1,471,480 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.67%	37
Remaining individualsnot grpmax-eligible	0.168%	596
Middle Easterngrpmax	0.0174%	5,758
European (non-Finnish)	0.015%	6,679
Admixed American	0.00523%	19,134

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Trp1441Cys
Coding: c.4323G>T
MANE Select: NM_001164496
dbSNP: rs200617587
Type: single nucleotide variant
Location: chr3:113326638 (GRCh38)
Gene constraint: LOEUF 0.697 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.87 · 1 PDB
Residue 1441: a UniProt-annotated variant site (in spgf20)

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

Similar variants

CFAP44 p.Glu463Ter Pathogenic ★★ same type
CFAP44 c.4759-3C>T Benign ★★ same type
CFAP44 p.Ala157= Benign ★★ same type
CFAP44 p.Ala486Val Likely benign ★★ ⚠ same type
CFAP44 p.Arg1059Gln Benign ★★ same type
CFAP44 p.Arg1495Trp Benign ★★ ⚠ same type
CFAP44 p.Arg1651Trp Benign/Likely benign ★★ ⚠ same type
CFAP44 p.Arg1806= Benign/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/cfap44-p-trp1441cys (accessed [today's date]).

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