Is INF2 p.Val970Met (c.2908G>A) pathogenic?

INF2 p.Val970Met (c.2908G>A) is classified Uncertain significance in INF2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-12-16). AlphaMissense: likely benign (0.201); Ultra-rare (popmax 0.0165%, mid); Associated with Charcot-Marie-Tooth disease dominant intermediate E.

How common is INF2 p.Val970Met (c.2908G>A) in the general population?

INF2 p.Val970Met (c.2908G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about INF2 p.Val970Met (c.2908G>A)?

AlphaMissense predicts likely benign (score 0.201) — an in-silico prediction, not a clinical call.

INF2 p.Val970Met

Q: What condition is associated with INF2 p.Val970Met (c.2908G>A)?

INF2 p.Val970Met (c.2908G>A) is associated with Charcot-Marie-Tooth disease dominant intermediate E, focal segmental glomerulosclerosis 5 (ClinVar).

Q: How is Autosomal dominant intermediate Charcot-Marie-Tooth disease type E inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

c.2908G>A · rs977752085 · VCV829916

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.201 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Charcot-Marie-Tooth disease dominant intermediate E

Computational evidence

Protein change
AlphaMissense	0.201	likely benign
REVEL	0.374	indeterminate
SaProt	LLR -9.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 3, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,931 bp · p 0.00089 · regional, not allelic
Overall
CADD	23.4	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 0.0165% Middle Eastern · 1/6,072 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,611,424 alleles · ultra-rare exomes 5/1,459,248 · genomes 3/152,176 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,072
European (non-Finnish)	0.000594%	168,488

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.Val970Met
Coding: c.2908G>A
MANE Select: NM_022489
dbSNP: rs977752085
Type: single nucleotide variant
Location: chr14:104713474 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB

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

Disease context

Charcot-Marie-Tooth disease dominant intermediate E — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: focal segmental glomerulosclerosis 5

For Autosomal dominant intermediate Charcot-Marie-Tooth disease type E (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: No data available

Similar variants

INF2 p.Val970= 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
INF2 p.Arg91Gly Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Asn202Asp 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-val970met (accessed [today's date]).

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