Is IFT54 p.Pro415Arg (c.1244C>G) pathogenic?

IFT54 p.Pro415Arg (c.1244C>G) is classified Conflicting classifications of pathogenicity in IFT54 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-10-08). AlphaMissense: likely benign (0.0829); Ultra-rare (popmax 0.0223%, eas).

How common is IFT54 p.Pro415Arg (c.1244C>G) in the general population?

IFT54 p.Pro415Arg (c.1244C>G) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about IFT54 p.Pro415Arg (c.1244C>G)?

AlphaMissense predicts likely benign (score 0.0829) — an in-silico prediction, not a clinical call.

IFT54 p.Pro415Arg

c.1244C>G · rs764563139 · VCV942702

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0829 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0829	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.1, phastCons 0.012
Regional constraint	o/e 0.94	unconstrained · MANE · 77 kb · p 0.082 · regional, not allelic
Overall
CADD	13.02	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 0.0223% East Asian · 10/44,902 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.000682% 11/1,613,980 alleles · ultra-rare exomes 9/1,461,814 · genomes 2/152,166 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,490
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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: IFT54
Protein: p.Pro415Arg
Coding: c.1244C>G
MANE Select: NM_015650
dbSNP: rs764563139
Type: single nucleotide variant
Location: chr2:238344581 (GRCh38)
Structure: AlphaFold pLDDT 61.95 · 2 PDB
Residue 415: the 'disordered' region; the 'disc1-interaction domain' region

Full IFT54 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRAF3IP1 p.Pro415= Likely benign ★ same residue
IFT54 c.1159+1G>C Likely pathogenic ★★ same type
IFT54 c.988-1G>A Likely pathogenic ★★ same type
IFT54 c.988-1G>C Likely pathogenic ★★ same type
IFT54 p.Arg565Ter Pathogenic/Likely pathogenic ★★ same type
IFT54 p.Trp572Ter Pathogenic/Likely pathogenic ★★ same type
IFT54 c.1452-5T>G Uncertain significance ★★ same type
IFT54 c.1910+3G>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/ift54-p-pro415arg (accessed [today's date]).

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