Is CFAP57 p.Pro67Ser (c.199C>T) pathogenic?

CFAP57 p.Pro67Ser (c.199C>T) is classified Uncertain significance in CFAP57 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-26). AlphaMissense: likely benign (0.1897); Ultra-rare (popmax 0.0143%, sas).

How common is CFAP57 p.Pro67Ser (c.199C>T) in the general population?

CFAP57 p.Pro67Ser (c.199C>T) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

What do computational predictors say about CFAP57 p.Pro67Ser (c.199C>T)?

AlphaMissense predicts likely benign (score 0.1897) — an in-silico prediction, not a clinical call.

CFAP57 p.Pro67Ser

c.199C>T · VCV4227060

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1897 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1897	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -8.83	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 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 81 kb · p 0.00012 · regional, not allelic
Overall
CADD	23.3	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 0.0143% South Asian · 13/91,080 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.000929% 15/1,614,194 alleles · ultra-rare exomes 15/1,461,888 · genomes 0/152,306 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	7,006
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Pro67Ser
Coding: c.199C>T
MANE Select: NM_001378189
Type: single nucleotide variant
Location: chr1:43181575 (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.Pro67Thr Uncertain significance ★ ⚠ same residue
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

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-pro67ser (accessed [today's date]).

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