Is CFAP57 p.Pro128Ser (c.382C>T) pathogenic?

CFAP57 p.Pro128Ser (c.382C>T) is classified Uncertain significance in CFAP57 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-07). AlphaMissense: likely benign (0.0703); Ultra-rare (popmax 0.0251%, nfe).

How common is CFAP57 p.Pro128Ser (c.382C>T) in the general population?

CFAP57 p.Pro128Ser (c.382C>T) is ultra-rare (popmax 0.0251%, nfe) (gnomAD).

What do computational predictors say about CFAP57 p.Pro128Ser (c.382C>T)?

AlphaMissense predicts likely benign (score 0.0703) — an in-silico prediction, not a clinical call.

CFAP57 p.Pro128Ser

c.382C>T · rs143229697 · VCV2365241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0703 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0251%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0703	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -6.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.9	GERP -0.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 81 kb · p 0.00012 · regional, not allelic
Overall
CADD	16.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0251% European (non-Finnish) · 296/1,180,030 alleles

Filtering AF 0.0227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0217%

Overall 0.0242% 391/1,614,162 alleles · ultra-rare exomes 364/1,461,874 · genomes 27/152,288 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.155%	644
Finnishnot grpmax-eligible	0.05%	2,001
European (non-Finnish)grpmax	0.0251%	3,987
Remaining individualsnot grpmax-eligible	0.0208%	4,808
Middle Eastern	0.0165%	6,062
South Asian	0.0022%	45,536
African / African-American	0.00133%	75,040

Ashkenazi Jewish 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.Pro128Ser
Coding: c.382C>T
MANE Select: NM_001378189
dbSNP: rs143229697
Type: single nucleotide variant
Location: chr1:43181758 (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-pro128ser (accessed [today's date]).

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