Is NEB p.Phe573Ser (c.1718T>C) pathogenic?

NEB p.Phe573Ser (c.1718T>C) is classified Uncertain significance in NEB (ClinVar, Single submitter, 2 submitters; last evaluated 2022-08-16). AlphaMissense: ambiguous (0.553); Very rare (popmax 0.00555%, sas); Associated with nemaline myopathy 2.

What condition is associated with NEB p.Phe573Ser (c.1718T>C)?

NEB p.Phe573Ser (c.1718T>C) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Phe573Ser (c.1718T>C) in the general population?

NEB p.Phe573Ser (c.1718T>C) is very rare (popmax 0.00555%, sas) (gnomAD).

How is Severe congenital nemaline myopathy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about NEB p.Phe573Ser (c.1718T>C)?

AlphaMissense predicts ambiguous (score 0.553) — an in-silico prediction, not a clinical call.

NEB p.Phe573Ser

c.1718T>C · rs767710795 · VCV969616

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.553 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00555%, sas)

Conditions

nemaline myopathy 2

Computational evidence

Protein change
AlphaMissense	0.553	ambiguous
REVEL	0.197	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 82 kb · p 0.26 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00555% South Asian · 5/90,050 alleles

Filtering AF 0.00212% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.000344% 5/1,453,228 alleles · very rare

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.Phe573Ser
Coding: c.1718T>C
MANE Select: NM_001164508
dbSNP: rs767710795
Type: single nucleotide variant
Location: chr2:151694586 (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

nemaline myopathy 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe congenital nemaline myopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

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
NEB c.22590+2T>C Uncertain significance ★★★ 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-phe573ser (accessed [today's date]).

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