Is CFAP54 p.Met1434Ile (c.4302G>C) pathogenic?

CFAP54 p.Met1434Ile (c.4302G>C) is classified Likely benign in CFAP54 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-01). AlphaMissense: ambiguous (0.4017); Rare (popmax 0.155%, mid).

How common is CFAP54 p.Met1434Ile (c.4302G>C) in the general population?

CFAP54 p.Met1434Ile (c.4302G>C) is rare (popmax 0.155%, mid) (gnomAD).

What do computational predictors say about CFAP54 p.Met1434Ile (c.4302G>C)?

AlphaMissense predicts ambiguous (score 0.4017) — an in-silico prediction, not a clinical call.

CFAP54 p.Met1434Ile

c.4302G>C · rs530120061 · VCV2672515

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4017 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.155%, mid)

Computational evidence

Protein change
AlphaMissense	0.4017	ambiguous
REVEL	0.017	moderately benign-leaning
Splicing
SpliceAI	Δ0.20	donor gain, 14 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.41	GERP -2, phastCons 0.023
Regional constraint	o/e 0.97	unconstrained · MANE · 327 kb · p 0.17 · regional, not allelic
Overall
CADD	1.57	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 0.155% Middle Eastern · 9/5,824 alleles

Filtering AF 0.0806% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0601%

Overall 0.0312% 465/1,491,324 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.719%	139
Middle Easterngrpmax	0.155%	647
Remaining individualsnot grpmax-eligible	0.098%	1,020
South Asian	0.0633%	1,581
Admixed American	0.0301%	3,326
European (non-Finnish)	0.0122%	8,217
African / African-American	0.00425%	23,544
Finnishnot grpmax-eligible	0.00228%	43,926

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.Met1434Ile
Coding: c.4302G>C
MANE Select: NM_001306084
dbSNP: rs530120061
Type: single nucleotide variant
Location: chr12:96630637 (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 p.Lys618Ter Conflicting classifications of pathogenicity ★ 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

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-met1434ile (accessed [today's date]).

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