Is CFAP43 p.Asp249Tyr (c.745G>T) pathogenic?

CFAP43 p.Asp249Tyr (c.745G>T) is classified Conflicting classifications of pathogenicity in CFAP43 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2020-02-01). AlphaMissense: likely benign (0.1929); Rare (popmax 0.388%, nfe).

How common is CFAP43 p.Asp249Tyr (c.745G>T) in the general population?

CFAP43 p.Asp249Tyr (c.745G>T) is rare (popmax 0.388%, nfe) (gnomAD).

What do computational predictors say about CFAP43 p.Asp249Tyr (c.745G>T)?

AlphaMissense predicts likely benign (score 0.1929) — an in-silico prediction, not a clinical call.

CFAP43 p.Asp249Tyr

c.745G>T · rs41291844 · VCV773520

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1929 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.388%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1929	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -6.25	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 1.2	GERP 1.9, phastCons 0.47
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 0.0013 · regional, not allelic
Overall
CADD	21.4	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 0.388% European (non-Finnish) · 4,569/1,178,940 alleles

Filtering AF 0.378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.374%

Overall 0.294% 4,743/1,610,538 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.388%	258
Remaining individualsnot grpmax-eligible	0.117%	854
Finnishnot grpmax-eligible	0.0672%	1,488
African / African-American	0.0655%	1,527
Middle Eastern	0.0165%	6,048
Admixed American	0.0119%	8,438
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,432

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: CFAP43
Protein: p.Asp249Tyr
Coding: c.745G>T
MANE Select: NM_025145
dbSNP: rs41291844
Type: single nucleotide variant
Location: chr10:104207815 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.27 · 1 PDB

Full CFAP43 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP43 p.Arg894Ter Pathogenic/Likely pathogenic ★★ same type
CFAP43 p.Thr1075Lys Uncertain significance ★★ ⚠ same type
CFAP43 c.2142-4A>G Benign ★★ same type
CFAP43 p.Glu1540Gly Benign/Likely benign ★★ same type
CFAP43 p.Leu1542Val Benign/Likely benign ★★ same type
CFAP43 p.Leu616Phe Benign ★★ ⚠ same type
CFAP43 p.Leu802= Benign ★★ same type
CFAP43 p.Pro246= Benign ★★ 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/cfap43-p-asp249tyr (accessed [today's date]).

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