Is CFAP74 p.Ser1444Thr (c.4331G>C) pathogenic?

CFAP74 p.Ser1444Thr (c.4331G>C) is classified Pathogenic in CFAP74 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-01-12). AlphaMissense: likely benign (0.1126); Ultra-rare (popmax 0.0468%, eas); Associated with ciliary dyskinesia, primary, 49, without situs inversus.

What condition is associated with CFAP74 p.Ser1444Thr (c.4331G>C)?

CFAP74 p.Ser1444Thr (c.4331G>C) is associated with ciliary dyskinesia, primary, 49, without situs inversus (ClinVar).

How common is CFAP74 p.Ser1444Thr (c.4331G>C) in the general population?

CFAP74 p.Ser1444Thr (c.4331G>C) is ultra-rare (popmax 0.0468%, eas) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CFAP74 p.Ser1444Thr (c.4331G>C)?

AlphaMissense predicts likely benign (score 0.1126) — an in-silico prediction, not a clinical call.

CFAP74 p.Ser1444Thr

c.4331G>C · rs755467514 · VCV2443734

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1126 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0468%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ciliary dyskinesia, primary, 49, without situs inversus

Computational evidence

Protein change
AlphaMissense	0.1126	likely benign ⚠ discordant with ClinVar
REVEL	0.137	moderately benign-leaning
SaProt	LLR -7.10	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 4.7	GERP 1.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	23.7	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 0.0468% East Asian · 21/44,880 alleles

Filtering AF 0.0313% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0263%

Overall 0.0013% 21/1,613,326 alleles · ultra-rare

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: CFAP74
Protein: p.Ser1444Thr
Coding: c.4331G>C
MANE Select: NM_001304360
dbSNP: rs755467514
Type: single nucleotide variant
Location: chr1:1923833 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.38
Residue 1444: a UniProt-annotated variant site (in cild49; uncertain significance)

Full CFAP74 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ciliary dyskinesia, primary, 49, without situs inversus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

CFAP74 p.Arg280Ter Likely pathogenic ★ same condition
CFAP74 p.Val768Gly Uncertain significance ★ ⚠ same condition
CFAP74 p.Arg218Trp Pathogenic ⚠ same condition
CFAP74 p.Asp1178Asn Pathogenic ⚠ same condition
CFAP74 p.Gly328Asp Pathogenic ⚠ same condition
CFAP74 p.Leu975fs Likely pathogenic ★★ same condition
CFAP74 p.Phe1461fs Pathogenic/Likely pathogenic ★★ same condition
CFAP74 p.Gly570fs Likely pathogenic ★ 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/cfap74-p-ser1444thr (accessed [today's date]).

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