Is CFAP57 p.Ser603= (c.1809G>A) pathogenic?

CFAP57 p.Ser603= (c.1809G>A) is classified Benign in CFAP57 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). Common (popmax 87.7%, nfe) — too common for a highly-penetrant pathogenic allele.

CFAP57 p.Ser603=

Q: How common is CFAP57 p.Ser603= (c.1809G>A) in the general population?

CFAP57 p.Ser603= (c.1809G>A) is common (popmax 87.7%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1809G>A · VCV4970475

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 87.7%, nfe) — too common for a highly-penetrant pathogenic allele

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 -7.5	GERP -3.7
Overall
CADD	0.072	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 87.7% European (non-Finnish) · 1,035,251/1,179,922 alleles

Filtering AF 87.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 87.5%

Overall 84% 1,355,815/1,613,788 alleles · common exomes 1,240,229/1,461,770 · genomes 115,586/152,018 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	92.1%	1
Ashkenazi Jewishnot grpmax-eligible	91.6%	1
European (non-Finnish)grpmax	87.7%	1
Middle Eastern	87.6%	1
Remaining individualsnot grpmax-eligible	83.4%	1
Finnishnot grpmax-eligible	81.6%	1
South Asian	75.5%	1
East Asian	74%	1
Admixed American	65%	2
African / African-American	56.1%	2

Amish 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: CFAP57
Protein: p.Ser603=
Coding: c.1809G>A
MANE Select: NM_001378189
Type: single nucleotide variant
Location: chr1:43209796 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 1 PDB
Residue 603: a UniProt-annotated variant site (found in a patient with primary ciliary dyskinesia; uncertain significance; loss of location to ciliary axoneme; reduced beat frequency)

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

Similar variants

CFAP57 p.Gln125Arg Likely benign ★★ ⚠ same type
CFAP57 p.Ile322Met Likely benign ★★ same type
CFAP57 p.Ser614= Likely benign ★★ same type
CFAP57 p.Arg411Ter Likely pathogenic ★ same type
CFAP57 p.Arg958Ter Pathogenic ★ same type
CFAP57 c.1929+122A>C Uncertain significance ★ same type
CFAP57 c.1929+139C>A Uncertain significance ★ same type
CFAP57 c.1929+154A>T 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/cfap57-p-ser603 (accessed [today's date]).

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