Is NEMF p.Pro584Ser (c.1750C>T) pathogenic?

NEMF p.Pro584Ser (c.1750C>T) is classified Uncertain significance in NEMF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-16). AlphaMissense: likely benign (0.0937); Ultra-rare (popmax 0.0263%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NEMF p.Pro584Ser (c.1750C>T)?

NEMF p.Pro584Ser (c.1750C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NEMF p.Pro584Ser (c.1750C>T) in the general population?

NEMF p.Pro584Ser (c.1750C>T) is ultra-rare (popmax 0.0263%, nfe) (gnomAD).

What do computational predictors say about NEMF p.Pro584Ser (c.1750C>T)?

AlphaMissense predicts likely benign (score 0.0937) — an in-silico prediction, not a clinical call.

NEMF p.Pro584Ser

c.1750C>T · rs368872377 · VCV3193304

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0937 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0263%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0937	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -8.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -0.12, phastCons 0.96
Regional constraint	o/e 0.37	unconstrained · MANE · 8,684 bp · p 5.1e-06 · regional, not allelic
Overall
CADD	21.3	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 0.0263% European (non-Finnish) · 310/1,177,732 alleles

Filtering AF 0.0239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.0204% 328/1,608,376 alleles · ultra-rare exomes 307/1,459,032 · genomes 21/149,344 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0263%	3,799
Remaining individualsnot grpmax-eligible	0.0177%	5,663
Ashkenazi Jewishnot grpmax-eligible	0.0102%	9,838
African / African-American	0.00542%	18,464

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: NEMF
Protein: p.Pro584Ser
Coding: c.1750C>T
MANE Select: NM_004713
dbSNP: rs368872377
Type: single nucleotide variant
Location: chr14:49806128 (GRCh38)
Gene constraint: LOEUF 0.687 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.96 · 2 PDB

Full NEMF 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

Similar variants

NEMF p.Pro584= Likely benign ★★ same residue
NEMF p.Arg934Ser Uncertain significance ★★ ⚠ same condition
NEMF p.Ile248Thr Uncertain significance ★★ ⚠ same condition
NEMF p.Ser785Pro Uncertain significance ★★ ⚠ same condition
NEMF p.Ala12Val Uncertain significance ★ ⚠ same condition
NEMF p.Ala142Val Uncertain significance ★ ⚠ same condition
NEMF p.Ala15Val Uncertain significance ★ ⚠ same condition
NEMF p.Ala295Val 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/nemf-p-pro584ser (accessed [today's date]).

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