Is CFAP57 p.Pro259= (c.777A>G) pathogenic?

CFAP57 p.Pro259= (c.777A>G) is classified Likely benign in CFAP57 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-02-14). Ultra-rare (popmax 0.0989%, afr); Associated with CFAP57-related disorder.

What condition is associated with CFAP57 p.Pro259= (c.777A>G)?

CFAP57 p.Pro259= (c.777A>G) is associated with CFAP57-related disorder (ClinVar).

How common is CFAP57 p.Pro259= (c.777A>G) in the general population?

CFAP57 p.Pro259= (c.777A>G) is ultra-rare (popmax 0.0989%, afr) (gnomAD).

CFAP57 p.Pro259=

c.777A>G · rs140557499 · VCV3040154

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0989%, afr)

Conditions

CFAP57-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.1	GERP -1.9
Overall
CADD	0.458	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0989% African / African-American · 74/74,790 alleles

Filtering AF 0.0808% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0741%

Overall 0.00899% 145/1,613,790 alleles · ultra-rare exomes 108/1,461,884 · genomes 37/151,906 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0989%	1,011
Remaining individualsnot grpmax-eligible	0.0144%	6,942
European (non-Finnish)	0.00517%	19,344
Admixed American	0.00167%	59,980

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: CFAP57
Protein: p.Pro259=
Coding: c.777A>G
MANE Select: NM_001378189
dbSNP: rs140557499
Type: single nucleotide variant
Location: chr1:43185164 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 1 PDB

Full CFAP57 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CFAP57-related disorder

Similar variants

CFAP57 c.1929+50G>A Conflicting classifications of pathogenicity ★ same condition
CFAP57 p.Ala145Val Uncertain significance ★ ⚠ same condition
CFAP57 p.Glu1035Asp Uncertain significance ★ ⚠ same condition
CFAP57 p.Ser584Ala Uncertain significance ★ ⚠ same condition
CFAP57 p.Arg1148Cys Uncertain significance ⚠ same condition
CFAP57 p.Gly394Ser Uncertain significance ⚠ same condition
CFAP57 p.Ile288Thr Uncertain significance ⚠ same condition
CFAP57 p.Met621Lys Uncertain significance ⚠ same condition

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/cfap57-p-pro259 (accessed [today's date]).

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