Is CFAP57 p.Arg464Cys (c.1390C>T) pathogenic?

CFAP57 p.Arg464Cys (c.1390C>T) is classified Uncertain significance in CFAP57 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-04). AlphaMissense: likely benign (0.3035); Very rare (popmax 0.00446%, eas).

How common is CFAP57 p.Arg464Cys (c.1390C>T) in the general population?

CFAP57 p.Arg464Cys (c.1390C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CFAP57 p.Arg464Cys (c.1390C>T)?

AlphaMissense predicts likely benign (score 0.3035) — an in-silico prediction, not a clinical call.

CFAP57 p.Arg464Cys

c.1390C>T · VCV4227054

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3035 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3035	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -12.52	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 81 kb · p 0.00012 · regional, not allelic
Overall
CADD	26.3	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 0.00446% East Asian · 2/44,874 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000868% 14/1,613,686 alleles · very rare exomes 13/1,461,736 · genomes 1/151,950 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,437
Remaining individualsnot grpmax-eligible	0.0016%	62,480
African / African-American	0.00134%	74,822
European (non-Finnish)	0.000848%	117,993

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.Arg464Cys
Coding: c.1390C>T
MANE Select: NM_001378189
Type: single nucleotide variant
Location: chr1:43198608 (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

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-arg464cys (accessed [today's date]).

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