Is NEB p.Ala396Val (c.1187C>T) pathogenic?

NEB p.Ala396Val (c.1187C>T) is classified Conflicting classifications of pathogenicity in NEB (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.2726); Ultra-rare (popmax 0.0362%, afr); Associated with Inborn genetic diseases.

What condition is associated with NEB p.Ala396Val (c.1187C>T)?

NEB p.Ala396Val (c.1187C>T) is associated with Inborn genetic diseases, nemaline myopathy 2 (ClinVar).

How common is NEB p.Ala396Val (c.1187C>T) in the general population?

NEB p.Ala396Val (c.1187C>T) is ultra-rare (popmax 0.0362%, afr) (gnomAD).

What do computational predictors say about NEB p.Ala396Val (c.1187C>T)?

AlphaMissense predicts likely benign (score 0.2726) — an in-silico prediction, not a clinical call.

NEB p.Ala396Val

c.1187C>T · rs369957704 · VCV573900

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2726 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0362%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2726	likely benign
REVEL	0.206	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 82 kb · p 0.26 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0362% African / African-American · 27/74,540 alleles

Filtering AF 0.0255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.022%

Overall 0.00199% 32/1,610,710 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0362%	2,761
Admixed American	0.00507%	19,741
Remaining individualsnot grpmax-eligible	0.00321%	31,157

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: NEB
Protein: p.Ala396Val
Coding: c.1187C>T
MANE Select: NM_001164508
dbSNP: rs369957704
Type: single nucleotide variant
Location: chr2:151697614 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)

Full NEB 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: nemaline myopathy 2

Similar variants

NEB p.Ala396fs Pathogenic ★ same residue
NEB c.11910+1G>A Likely pathogenic ★★★ same condition
NEB c.6076-1G>T Likely pathogenic ★★★ same condition
NEB c.78+1G>A Pathogenic ★★★ same condition
NEB p.Arg2313Ter Pathogenic ★★★ same condition
NEB p.Asp498Gly Likely pathogenic ★★★ ⚠ same condition
NEB p.Ser6366Ile Pathogenic ★★★ same condition
NEB p.Ser6648= 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/neb-p-ala396val (accessed [today's date]).

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