Is CFAP54 p.Lys618Ter (c.1852A>T) pathogenic?

CFAP54 p.Lys618Ter (c.1852A>T) is classified Conflicting classifications of pathogenicity in CFAP54 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-03-14). Ultra-rare (popmax 0.044%, nfe).

How common is CFAP54 p.Lys618Ter (c.1852A>T) in the general population?

CFAP54 p.Lys618Ter (c.1852A>T) is ultra-rare (popmax 0.044%, nfe) (gnomAD).

CFAP54 p.Lys618Ter

c.1852A>T · VCV3702596

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.044%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 68
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.044% European (non-Finnish) · 505/1,146,760 alleles

Filtering AF 0.0408% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0395%

Overall 0.0378% 581/1,536,048 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0594%	1,685
Remaining individualsnot grpmax-eligible	0.045%	2,224
European (non-Finnish)grpmax	0.044%	2,271
South Asian	0.0286%	3,502
Finnishnot grpmax-eligible	0.00673%	14,856
African / African-American	0.00547%	18,296
Admixed American	0.00196%	50,998

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: CFAP54
Protein: p.Lys618Ter
Coding: c.1852A>T
MANE Select: NM_001306084
Type: single nucleotide variant
Location: chr12:96538444 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 (gnomAD)

Full CFAP54 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP54 p.Pro22= Likely benign ★★ same type
CFAP54 p.Gln649Ter Likely pathogenic ★ same type
CFAP54 p.Arg915Gln Uncertain significance ★ ⚠ same type
CFAP54 p.Asn992Asp Uncertain significance ★ ⚠ same type
CFAP54 c.9171+4T>C Likely benign ★ same type
CFAP54 p.Arg1020Trp Likely benign ★ same type
CFAP54 p.Arg1216His Likely benign ★ same type
CFAP54 p.Met1434Ile Likely benign ★ 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/cfap54-p-lys618ter (accessed [today's date]).

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