Is NEMF p.Ser785Pro (c.2353T>C) pathogenic?

NEMF p.Ser785Pro (c.2353T>C) is classified Uncertain significance in NEMF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-04). AlphaMissense: likely benign (0.2174); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with NEMF p.Ser785Pro (c.2353T>C)?

NEMF p.Ser785Pro (c.2353T>C) is associated with Inborn genetic diseases, intellectual developmental disorder with speech delay and axonal peripheral neuropathy (ClinVar).

How common is NEMF p.Ser785Pro (c.2353T>C) in the general population?

NEMF p.Ser785Pro (c.2353T>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about NEMF p.Ser785Pro (c.2353T>C)?

AlphaMissense predicts likely benign (score 0.2174) — an in-silico prediction, not a clinical call.

NEMF p.Ser785Pro

c.2353T>C · rs756795071 · VCV2391665

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2174 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2174	likely benign
REVEL	0.264	benign-leaning
SaProt	LLR -7.58	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 9.3	GERP 0.47, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 21 kb · p 0.053 · regional, not allelic
Overall
CADD	25.8	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 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00112% 18/1,612,722 alleles · ultra-rare exomes 15/1,460,566 · genomes 3/152,156 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Admixed American	0.00334%	29,914
Remaining individualsnot grpmax-eligible	0.0016%	62,442
European (non-Finnish)	0.00119%	84,238

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.Ser785Pro
Coding: c.2353T>C
MANE Select: NM_004713
dbSNP: rs756795071
Type: single nucleotide variant
Location: chr14:49800439 (GRCh38)
Gene constraint: LOEUF 0.687 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.96 · 2 PDB
Residue 785: a UniProt-annotated variant site (in iddsapn); the 'disordered' region; an α-helix

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

Also linked: intellectual developmental disorder with speech delay and axonal peripheral neuropathy

Similar variants

NEMF p.Arg671Ter Pathogenic ★★ same condition
NEMF p.Tyr470Ter Pathogenic ★★ same condition
NEMF p.Arg934Ser Uncertain significance ★★ ⚠ same condition
NEMF p.Ile248Thr Uncertain significance ★★ ⚠ same condition
NEMF p.Pro584Ser Uncertain significance ★★ ⚠ same condition
NEMF c.2096-2A>G Likely pathogenic ★ same condition
NEMF c.807-2A>C Likely pathogenic ★ same condition
NEMF p.Gln356Ter 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/nemf-p-ser785pro (accessed [today's date]).

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