Is NEMF p.Thr239Pro (c.715A>C) pathogenic?

NEMF p.Thr239Pro (c.715A>C) is classified Uncertain significance in NEMF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-10). AlphaMissense: ambiguous (0.4558); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with NEMF p.Thr239Pro (c.715A>C)?

NEMF p.Thr239Pro (c.715A>C) is associated with Inborn genetic diseases (ClinVar).

How common is NEMF p.Thr239Pro (c.715A>C) in the general population?

NEMF p.Thr239Pro (c.715A>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about NEMF p.Thr239Pro (c.715A>C)?

AlphaMissense predicts ambiguous (score 0.4558) — an in-silico prediction, not a clinical call.

NEMF p.Thr239Pro

c.715A>C · VCV3878832

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4558 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4558	ambiguous
REVEL	0.181	moderately benign-leaning
SaProt	LLR -9.55	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.3	GERP -1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 38 kb · p 0.049 · regional, not allelic
Overall
CADD	22.3	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 0.00134% African / African-American · 1/74,596 alleles

Overall 0.000657% 1/152,226 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: NEMF
Protein: p.Thr239Pro
Coding: c.715A>C
MANE Select: NM_004713
Type: single nucleotide variant
Location: chr14:49833443 (GRCh38)
Gene constraint: LOEUF 0.687 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.96 · 2 PDB
Residue 239: 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

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-thr239pro (accessed [today's date]).

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