Is CFAP73 p.Tyr8Cys (c.23A>G) pathogenic?

CFAP73 p.Tyr8Cys (c.23A>G) is classified Uncertain significance in CFAP73 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). AlphaMissense: ambiguous (0.4896); Ultra-rare (popmax 0.0356%, afr).

How common is CFAP73 p.Tyr8Cys (c.23A>G) in the general population?

CFAP73 p.Tyr8Cys (c.23A>G) is ultra-rare (popmax 0.0356%, afr) (gnomAD).

What do computational predictors say about CFAP73 p.Tyr8Cys (c.23A>G)?

AlphaMissense predicts ambiguous (score 0.4896) — an in-silico prediction, not a clinical call.

CFAP73 p.Tyr8Cys

c.23A>G · rs373892417 · VCV2375445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4896 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0356%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4896	ambiguous · top 7% in CFAP73
REVEL	0.261	benign-leaning
SaProt	LLR -7.86	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 5.7	GERP 0.92, phastCons 0.93
Regional constraint	o/e 0.95	unconstrained · MANE · 7,818 bp · p 0.33 · regional, not allelic
Overall
CADD	23.5	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 0.0356% African / African-American · 26/73,032 alleles

Filtering AF 0.0249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0213%

Overall 0.00168% 26/1,551,240 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: CFAP73
Protein: p.Tyr8Cys
Coding: c.23A>G
MANE Select: NM_001144872
dbSNP: rs373892417
Type: single nucleotide variant
Location: chr12:113149880 (GRCh38)
Gene constraint: LOEUF 1.354 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.57 · 1 PDB

Full CFAP73 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX54 p.Gly875Asp Uncertain significance ★★ ⚠ same type
CFAP73 p.Ala103Val Uncertain significance ★ ⚠ same type
CFAP73 p.Ala109Gly Uncertain significance ★ ⚠ same type
CFAP73 p.Ala150Glu Uncertain significance ★ ⚠ same type
CFAP73 p.Ala171Thr Uncertain significance ★ ⚠ same type
CFAP73 p.Ala175Val Uncertain significance ★ ⚠ same type
CFAP73 p.Ala186Ser Uncertain significance ★ ⚠ same type
CFAP73 p.Ala214Thr 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/cfap73-p-tyr8cys (accessed [today's date]).

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