Is NTF4 p.Ala71Val (c.212C>T) pathogenic?

NTF4 p.Ala71Val (c.212C>T) is classified Uncertain significance in NTF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely benign (0.0897); Very rare (popmax 0.00026%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NTF4 p.Ala71Val (c.212C>T)?

NTF4 p.Ala71Val (c.212C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NTF4 p.Ala71Val (c.212C>T) in the general population?

NTF4 p.Ala71Val (c.212C>T) is very rare (popmax 0.00026%, nfe) (gnomAD).

What do computational predictors say about NTF4 p.Ala71Val (c.212C>T)?

AlphaMissense predicts likely benign (score 0.0897) — an in-silico prediction, not a clinical call.

NTF4 p.Ala71Val

c.212C>T · VCV4626551

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0897 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00026%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0897	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -7.79	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 -0.032
Regional constraint	o/e 0.89	unconstrained · MANE · 629 bp · p 0.054 · regional, not allelic
Overall
CADD	2.303	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 0.00026% European (non-Finnish) · 3/1,152,756 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000192% 3/1,559,472 alleles · very rare exomes 2/1,407,236 · genomes 1/152,236 · 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: NTF4
Protein: p.Ala71Val
Coding: c.212C>T
MANE Select: NM_006179
Type: single nucleotide variant
Location: chr19:49061786 (GRCh38)
Gene constraint: LOEUF 1.493 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 78.69 · 3 PDB

Full NTF4 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

NTF4 p.Gln174Arg Likely pathogenic ★ same condition
NTF4 p.Ala127Ser Uncertain significance ★ ⚠ same condition
NTF4 p.Ala172Thr Uncertain significance ★ ⚠ same condition
NTF4 p.Ala54Thr Uncertain significance ★ ⚠ same condition
NTF4 p.Ala73Val Uncertain significance ★ ⚠ same condition
NTF4 p.Arg107His Uncertain significance ★ ⚠ same condition
NTF4 p.Arg108Gln Uncertain significance ★ ⚠ same condition
NTF4 p.Arg108Trp 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/ntf4-p-ala71val (accessed [today's date]).

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