Is CFAP45 p.Arg513His (c.1538G>A) pathogenic?

CFAP45 p.Arg513His (c.1538G>A) is classified Uncertain significance in CFAP45 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-14). AlphaMissense: likely benign (0.0795); Ultra-rare (popmax 0.0274%, sas).

How common is CFAP45 p.Arg513His (c.1538G>A) in the general population?

CFAP45 p.Arg513His (c.1538G>A) is ultra-rare (popmax 0.0274%, sas) (gnomAD).

What do computational predictors say about CFAP45 p.Arg513His (c.1538G>A)?

AlphaMissense predicts likely benign (score 0.0795) — an in-silico prediction, not a clinical call.

CFAP45 p.Arg513His

c.1538G>A · rs142022446 · VCV2208092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0795 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0274%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0795	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -9.19	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 1.1	GERP 1.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 28 kb · p 0.64 · regional, not allelic
Overall
CADD	25.2	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 0.0274% South Asian · 25/91,086 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.0127% 205/1,614,234 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0274%	3,643
European (non-Finnish)	0.014%	7,152
Remaining individualsnot grpmax-eligible	0.0096%	10,418
Admixed American	0.00666%	15,006
East Asian	0.00446%	22,440
African / African-American	0.004%	25,022

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: CFAP45
Protein: p.Arg513His
Coding: c.1538G>A
MANE Select: NM_012337
dbSNP: rs142022446
Type: single nucleotide variant
Location: chr1:159872983 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 2 PDB
Residue 513: 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

Similar variants

CFAP45 p.Arg513Cys Uncertain significance ★ ⚠ same residue
CFAP45 p.Arg513Leu Uncertain significance ★ ⚠ same residue
CFAP45 p.Asp320Tyr Uncertain significance ★★ ⚠ same type
CFAP45 p.Lys518Glu Uncertain significance ★★ ⚠ same type
CFAP45 p.Asp222Gly Benign ★★ same type
CFAP45 p.Arg350Ter Likely pathogenic ★ same type
CFAP45 p.Ala15Pro Uncertain significance ★ ⚠ same type
CFAP45 p.Ala370Pro 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-arg513his (accessed [today's date]).

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