Is NEMF p.Pro645Ser (c.1933C>T) pathogenic?

NEMF p.Pro645Ser (c.1933C>T) is classified Uncertain significance in NEMF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). AlphaMissense: likely pathogenic (0.6172); Ultra-rare (popmax 0.0112%, eas); Associated with Inborn genetic diseases.

What condition is associated with NEMF p.Pro645Ser (c.1933C>T)?

NEMF p.Pro645Ser (c.1933C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NEMF p.Pro645Ser (c.1933C>T) in the general population?

NEMF p.Pro645Ser (c.1933C>T) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

What do computational predictors say about NEMF p.Pro645Ser (c.1933C>T)?

AlphaMissense predicts likely pathogenic (score 0.6172) — an in-silico prediction, not a clinical call.

NEMF p.Pro645Ser

c.1933C>T · VCV3299276

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6172 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6172	likely pathogenic
REVEL	0.386	indeterminate
SaProt	LLR -8.29	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.30	donor loss · deltas
Pangolin	Δ0.29	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.9	GERP 0.69, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 21 kb · p 0.053 · regional, not allelic
Overall
CADD	29.1	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 0.0112% East Asian · 5/44,818 alleles

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

Overall 0.000343% 5/1,458,240 alleles · ultra-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: NEMF
Protein: p.Pro645Ser
Coding: c.1933C>T
MANE Select: NM_004713
Type: single nucleotide variant
Location: chr14:49802710 (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.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
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-pro645ser (accessed [today's date]).

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