Is CFAP45 p.Asp35Asn (c.103G>A) pathogenic?

CFAP45 p.Asp35Asn (c.103G>A) is classified Uncertain significance in CFAP45 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). AlphaMissense: ambiguous (0.489); Very rare (popmax 0.00133%, afr).

How common is CFAP45 p.Asp35Asn (c.103G>A) in the general population?

CFAP45 p.Asp35Asn (c.103G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CFAP45 p.Asp35Asn (c.103G>A)?

AlphaMissense predicts ambiguous (score 0.489) — an in-silico prediction, not a clinical call.

CFAP45 p.Asp35Asn

c.103G>A · VCV3491299

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.489 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.489	ambiguous
REVEL	0.173	moderately benign-leaning
SaProt	LLR -6.68	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 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 28 kb · p 0.64 · regional, not allelic
Overall
CADD	27.9	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 · 1/75,046 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000479% 7/1,461,706 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,046
European (non-Finnish)	0.000508%	196,659

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.Asp35Asn
Coding: c.103G>A
MANE Select: NM_012337
Type: single nucleotide variant
Location: chr1:159893206 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 2 PDB

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

Similar variants

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
CFAP45 p.Ala436Val Uncertain significance ★ ⚠ same type
CFAP45 p.Ala69Thr 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-asp35asn (accessed [today's date]).

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