Is IFT52 p.Glu4Asp (c.12G>C) pathogenic?

IFT52 p.Glu4Asp (c.12G>C) is classified Uncertain significance in IFT52 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-15). AlphaMissense: likely benign (0.0508); Ultra-rare (popmax 0.0603%, afr).

How common is IFT52 p.Glu4Asp (c.12G>C) in the general population?

IFT52 p.Glu4Asp (c.12G>C) is ultra-rare (popmax 0.0603%, afr) (gnomAD).

What do computational predictors say about IFT52 p.Glu4Asp (c.12G>C)?

AlphaMissense predicts likely benign (score 0.0508) — an in-silico prediction, not a clinical call.

IFT52 p.Glu4Asp

c.12G>C · rs138787768 · VCV1409424

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0508 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0603%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0508	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -6.31	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 0.092	GERP -3.8, phastCons 0.033
Regional constraint	o/e 0.86	unconstrained · MANE · 52 kb · p 0.0018 · regional, not allelic
Overall
CADD	6.844	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 0.0603% African / African-American · 45/74,610 alleles

Filtering AF 0.0462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0414%

Overall 0.00333% 53/1,591,416 alleles · ultra-rare exomes 21/1,439,148 · genomes 32/152,268 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0603%	1,658
Middle Eastern	0.0166%	6,018
Admixed American	0.00501%	19,977
Remaining individualsnot grpmax-eligible	0.00324%	30,866
South Asian	0.00221%	45,271

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: IFT52
Protein: p.Glu4Asp
Coding: c.12G>C
MANE Select: NM_016004
dbSNP: rs138787768
Type: single nucleotide variant
Location: chr20:43594710 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21

Full IFT52 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IFT52 p.Glu4= Likely benign ★ same residue
IFT52 p.Asn35Ser Uncertain significance ★★ ⚠ same type
IFT52 p.Gly134Glu Uncertain significance ★★ ⚠ same type
IFT52 p.Leu164Phe Uncertain significance ★★ ⚠ same type
IFT52 p.Leu334Arg Uncertain significance ★★ same type
IFT52 p.Phe95Ser Uncertain significance ★★ ⚠ same type
IFT52 p.Pro397Ser Uncertain significance ★★ ⚠ same type
IFT52 p.Val53Met 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/ift52-p-glu4asp (accessed [today's date]).

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