Is IFT52 p.Ala337= (c.1011G>A) pathogenic?

IFT52 p.Ala337= (c.1011G>A) is classified Benign in IFT52 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Low-frequency (popmax 3.59%, mid).

How common is IFT52 p.Ala337= (c.1011G>A) in the general population?

IFT52 p.Ala337= (c.1011G>A) is low-frequency (popmax 3.59%, mid) (gnomAD).

IFT52 p.Ala337=

c.1011G>A · rs41296223 · VCV1229501

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.59%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.71	donor gain · deltas
Pangolin	Δ0.35	gain · loss 0.18 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.32	GERP -4.7, phastCons 0.013
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.59% Middle Eastern · 216/6,022 alleles

Filtering AF 3.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.31%

Overall 3.08% 49,677/1,613,890 alleles · low-frequency exomes 45,570/1,461,560 · genomes 4,107/152,330 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	6.29%	16
Finnishnot grpmax-eligible	5.81%	17
Middle Easterngrpmax	3.59%	28
Remaining individualsnot grpmax-eligible	3.38%	30
European (non-Finnish)	3.35%	30
Amishnot grpmax-eligible	1.97%	51
Admixed American	1.71%	59
South Asian	0.815%	123
African / African-American	0.601%	166
East Asian	0.00668%	14,962

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: IFT52
Protein: p.Ala337=
Coding: c.1011G>A
MANE Select: NM_016004
dbSNP: rs41296223
Type: single nucleotide variant
Location: chr20:43636013 (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.Ala337Val Uncertain significance ★ ⚠ same residue
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

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-ala337 (accessed [today's date]).

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