Is NEMF p.Ala797Pro (c.2389G>C) pathogenic?

NEMF p.Ala797Pro (c.2389G>C) is classified Uncertain significance in NEMF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0674); Ultra-rare (popmax 0.0112%, eas); Associated with Inborn genetic diseases.

What condition is associated with NEMF p.Ala797Pro (c.2389G>C)?

NEMF p.Ala797Pro (c.2389G>C) is associated with Inborn genetic diseases (ClinVar).

How common is NEMF p.Ala797Pro (c.2389G>C) in the general population?

NEMF p.Ala797Pro (c.2389G>C) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

What do computational predictors say about NEMF p.Ala797Pro (c.2389G>C)?

AlphaMissense predicts likely benign (score 0.0674) — an in-silico prediction, not a clinical call.

NEMF p.Ala797Pro

c.2389G>C · VCV4118790

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0674 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0674	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -5.27	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 -0.18	GERP -2.5, phastCons 0.001
Regional constraint	o/e 0.92	unconstrained · MANE · 21 kb · p 0.053 · regional, not allelic
Overall
CADD	12.71	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 0.0112% East Asian · 5/44,830 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00031% 5/1,612,036 alleles · ultra-rare exomes 5/1,459,798 · genomes 0/152,238 · joint denominator

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.Ala797Pro
Coding: c.2389G>C
MANE Select: NM_004713
Type: single nucleotide variant
Location: chr14:49799662 (GRCh38)
Gene constraint: LOEUF 0.687 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.96 · 2 PDB
Residue 797: a UniProt-annotated variant site (in iddsapn); the 'disordered' region

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.Ala797Thr Uncertain significance ★ ⚠ same residue
NEMF p.Arg934Ser Uncertain significance ★★ ⚠ same condition
NEMF p.Ile248Thr Uncertain significance ★★ ⚠ same condition
NEMF p.Pro584Ser 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

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-ala797pro (accessed [today's date]).

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