Is INF2 p.Ala949= (c.2847G>A) pathogenic?

INF2 p.Ala949= (c.2847G>A) is classified Conflicting classifications of pathogenicity in INF2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-17). Ultra-rare (popmax 0.0268%, eas); Associated with Inborn genetic diseases.

What condition is associated with INF2 p.Ala949= (c.2847G>A)?

INF2 p.Ala949= (c.2847G>A) is associated with Inborn genetic diseases, focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Ala949= (c.2847G>A) in the general population?

INF2 p.Ala949= (c.2847G>A) is ultra-rare (popmax 0.0268%, eas) (gnomAD).

INF2 p.Ala949=

c.2847G>A · rs754546219 · VCV540058

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0268%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.9	GERP -5.5
Overall
CADD	0.745	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0268% East Asian · 11/40,992 alleles

Filtering AF 0.015% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0116%

Overall 0.00355% 55/1,550,576 alleles · ultra-rare exomes 49/1,398,278 · genomes 6/152,298 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0268%	3,727
Admixed American	0.00979%	10,214
Remaining individualsnot grpmax-eligible	0.00666%	15,020
South Asian	0.00475%	21,065
European (non-Finnish)	0.00261%	38,254
African / African-American	0.00137%	73,168

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: INF2
Protein: p.Ala949=
Coding: c.2847G>A
MANE Select: NM_022489
dbSNP: rs754546219
Type: single nucleotide variant
Location: chr14:104713278 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 949: the 'disordered' region

Full INF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: focal segmental glomerulosclerosis 5 Charcot-Marie-Tooth disease dominant intermediate E

Similar variants

INF2 p.Ala949Thr Uncertain significance ★★ ⚠ same residue
INF2 p.Ala949Val Conflicting classifications of pathogenicity ★ ⚠ same residue
INF2 p.Ala949Gly Likely benign ★ same residue
INF2 p.Arg177Cys Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg214Cys Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg214His Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg218Gln Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg218Trp Pathogenic/Likely pathogenic ★★ same condition

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/inf2-p-ala949 (accessed [today's date]).

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