Is IFT54 p.Ser623= (c.1869C>T) pathogenic?

IFT54 p.Ser623= (c.1869C>T) is classified Likely benign in IFT54 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-24). Very rare (popmax 0.000763%, nfe).

How common is IFT54 p.Ser623= (c.1869C>T) in the general population?

IFT54 p.Ser623= (c.1869C>T) is very rare (popmax 0.000763%, nfe) (gnomAD).

IFT54 p.Ser623=

c.1869C>T · rs201903517 · VCV1427024

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.49	donor gain · deltas
Constraint at this position
Conservation	phyloP -20	GERP -2.7
Overall
CADD	11.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,179,216 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000683% 11/1,610,412 alleles · very rare exomes 11/1,460,122 · genomes 0/150,290 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,558
Finnishnot grpmax-eligible	0.0016%	62,410
European (non-Finnish)grpmax	0.000763%	131,024

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: IFT54
Protein: p.Ser623=
Coding: c.1869C>T
MANE Select: NM_015650
dbSNP: rs201903517
Type: single nucleotide variant
Location: chr2:238397638 (GRCh38)
Structure: AlphaFold pLDDT 61.95 · 2 PDB
Residue 623: the 'disc1-interaction domain' region

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

Similar variants

TRAF3IP1 p.Ser623Arg Uncertain significance ★ ⚠ 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-ser623 (accessed [today's date]).

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