Is CFAP45 p.Asp320Tyr (c.958G>T) pathogenic?

CFAP45 p.Asp320Tyr (c.958G>T) is classified Uncertain significance in CFAP45 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-17). AlphaMissense: likely benign (0.2); Very rare (popmax 0.00133%, afr).

How common is CFAP45 p.Asp320Tyr (c.958G>T) in the general population?

CFAP45 p.Asp320Tyr (c.958G>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CFAP45 p.Asp320Tyr (c.958G>T)?

AlphaMissense predicts likely benign (score 0.2) — an in-silico prediction, not a clinical call.

CFAP45 p.Asp320Tyr

c.958G>T · rs1365860809 · VCV2511673

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -11.61	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 28 kb · p 0.64 · regional, not allelic
Overall
CADD	24.5	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 0.00133% African / African-American · 1/74,910 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000744% 12/1,613,896 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,827
African / African-Americangrpmax	0.00133%	74,910
European (non-Finnish)	0.000678%	147,495

Remaining individuals 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: CFAP45
Protein: p.Asp320Tyr
Coding: c.958G>T
MANE Select: NM_012337
dbSNP: rs1365860809
Type: single nucleotide variant
Location: chr1:159880640 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 2 PDB
Residue 320: 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.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
CFAP45 p.Ala436Val Uncertain significance ★ ⚠ same type
CFAP45 p.Ala69Thr Uncertain significance ★ ⚠ same type
CFAP45 p.Ala6Ser 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-asp320tyr (accessed [today's date]).

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