Is SBF2 p.Val657= (c.1971A>G) pathogenic?

SBF2 p.Val657= (c.1971A>G) is classified Conflicting classifications of pathogenicity in SBF2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0178%, eas); Associated with Inborn genetic diseases.

What condition is associated with SBF2 p.Val657= (c.1971A>G)?

SBF2 p.Val657= (c.1971A>G) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4B2, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is SBF2 p.Val657= (c.1971A>G) in the general population?

SBF2 p.Val657= (c.1971A>G) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

SBF2 p.Val657=

c.1971A>G · rs368639697 · VCV306603

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.024	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -5.4	GERP -4.2
Overall
CADD	0.223	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,902 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00192% 31/1,614,086 alleles · ultra-rare exomes 28/1,461,876 · genomes 3/152,210 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.032%	3,125
East Asiangrpmax	0.0178%	5,613
Admixed American	0.00333%	30,006
European (non-Finnish)	8.47e-05%	1,180,022

Remaining individuals 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: SBF2
Protein: p.Val657=
Coding: c.1971A>G
MANE Select: NM_030962
dbSNP: rs368639697
Type: single nucleotide variant
Location: chr11:9858355 (GRCh38)

Full SBF2 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: Charcot-Marie-Tooth disease type 4B2 Charcot-Marie-Tooth disease type 4

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/sbf2-p-val657 (accessed [today's date]).

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