Is IFT52 p.Phe95Ser (c.284T>C) pathogenic?

IFT52 p.Phe95Ser (c.284T>C) is classified Uncertain significance in IFT52 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-07). AlphaMissense: likely benign (0.2389); Very rare (popmax 0.000528%, nfe).

How common is IFT52 p.Phe95Ser (c.284T>C) in the general population?

IFT52 p.Phe95Ser (c.284T>C) is very rare (popmax 0.000528%, nfe) (gnomAD).

What do computational predictors say about IFT52 p.Phe95Ser (c.284T>C)?

AlphaMissense predicts likely benign (score 0.2389) — an in-silico prediction, not a clinical call.

IFT52 p.Phe95Ser

c.284T>C · rs1167177237 · VCV1523815

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2389 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000528%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2389	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -11.07	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.3	phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 52 kb · p 0.0018 · regional, not allelic
Overall
CADD	20.5	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 0.000528% European (non-Finnish) · 6/1,137,040 alleles

Filtering AF 0.00019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000125%

Overall 0.000384% 6/1,563,760 alleles · very rare exomes 4/1,411,556 · genomes 2/152,204 · 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.Phe95Ser
Coding: c.284T>C
MANE Select: NM_016004
dbSNP: rs1167177237
Type: single nucleotide variant
Location: chr20:43603836 (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.Pro397Ser Uncertain significance ★★ ⚠ same type
IFT52 p.Val53Met Uncertain significance ★★ ⚠ same type
IFT52 c.1011+73T>C 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/ift52-p-phe95ser (accessed [today's date]).

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