Is CFAP45 p.Lys518Glu (c.1552A>G) pathogenic?

CFAP45 p.Lys518Glu (c.1552A>G) is classified Uncertain significance in CFAP45 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-07). AlphaMissense: ambiguous (0.503); Absent from gnomAD v4.1; Associated with heterotaxy, visceral, 11, autosomal, with male infertility.

What condition is associated with CFAP45 p.Lys518Glu (c.1552A>G)?

CFAP45 p.Lys518Glu (c.1552A>G) is associated with heterotaxy, visceral, 11, autosomal, with male infertility (ClinVar).

How common is CFAP45 p.Lys518Glu (c.1552A>G) in the general population?

CFAP45 p.Lys518Glu (c.1552A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFAP45 p.Lys518Glu (c.1552A>G)?

AlphaMissense predicts ambiguous (score 0.503) — an in-silico prediction, not a clinical call.

CFAP45 p.Lys518Glu

c.1552A>G · rs2525089145 · VCV2618750

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.503 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

heterotaxy, visceral, 11, autosomal, with male infertility

Computational evidence

Protein change
AlphaMissense	0.503	ambiguous
REVEL	0.268	benign-leaning
SaProt	LLR -15.87	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 28 kb · p 0.64 · regional, not allelic
Overall
CADD	25.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFAP45
Protein: p.Lys518Glu
Coding: c.1552A>G
MANE Select: NM_012337
dbSNP: rs2525089145
Type: single nucleotide variant
Location: chr1:159872969 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 2 PDB
Residue 518: the trichohyalin-plectin-homology domain; a UniProt-annotated variant site (in htx11; loss of panaxonemal expression in respiratory cilia and in sperm flagella)

Full CFAP45 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

heterotaxy, visceral, 11, autosomal, with male infertility — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP45 p.Arg350Ter Likely pathogenic ★ same condition
CFAP45 p.Arg303Ter Pathogenic same condition
CFAP45 p.Gln241Ter Pathogenic same condition
CFAP45 p.Gln491fs Pathogenic ★ same condition
CFAP45 p.Gln151fs Pathogenic same condition
CFAP45 p.Asp320Tyr Uncertain significance ★★ ⚠ same type
CFAP45 p.Asp222Gly Benign ★★ ⚠ same type
CFAP45 p.Ala15Pro Uncertain significance ★ ⚠ 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/cfap45-p-lys518glu (accessed [today's date]).

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