Is IFT52 p.Ser342Arg (c.1026T>A) pathogenic?

IFT52 p.Ser342Arg (c.1026T>A) is classified Uncertain significance in IFT52 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-23). AlphaMissense: ambiguous (0.3992); Very rare (popmax 0.005%, amr).

How common is IFT52 p.Ser342Arg (c.1026T>A) in the general population?

IFT52 p.Ser342Arg (c.1026T>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about IFT52 p.Ser342Arg (c.1026T>A)?

AlphaMissense predicts ambiguous (score 0.3992) — an in-silico prediction, not a clinical call.

IFT52 p.Ser342Arg

c.1026T>A · rs973090222 · VCV1989454

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3992 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Computational evidence

Protein change
AlphaMissense	0.3992	ambiguous
REVEL	0.32	indeterminate
SaProt	LLR -7.21	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.24	GERP -4.4, phastCons 0.99
Regional constraint	o/e 0.86	unconstrained · MANE · 52 kb · p 0.0018 · regional, not allelic
Overall
CADD	12.09	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 0.005% Admixed American · 3/59,942 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000186% 3/1,610,766 alleles · very rare exomes 3/1,458,420 · genomes 0/152,346 · joint denominator

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.Ser342Arg
Coding: c.1026T>A
MANE Select: NM_016004
dbSNP: rs973090222
Type: single nucleotide variant
Location: chr20:43637159 (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.Asn35Ser Uncertain significance ★★ ⚠ same type
IFT52 p.Glu4Asp 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-ser342arg (accessed [today's date]).

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