Is MTHFR p.Phe384fs (c.1151_1152delinsG) pathogenic?

MTHFR p.Phe384fs (c.11511152delinsG) is classified Likely pathogenic in MTHFR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-02). Absent from gnomAD; Associated with neural tube defects, folate-sensitive.

What condition is associated with MTHFR p.Phe384fs (c.1151_1152delinsG)?

MTHFR p.Phe384fs (c.1151_1152delinsG) is associated with neural tube defects, folate-sensitive (ClinVar).

How common is MTHFR p.Phe384fs (c.1151_1152delinsG) in the general population?

MTHFR p.Phe384fs (c.1151_1152delinsG) is absent from gnomAD (gnomAD).

MTHFR p.Phe384fs

c.1151_1152delinsG · rs2522873347 · VCV2676837

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

neural tube defects, folate-sensitive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP -0.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MTHFR
Protein: p.Phe384fs
Coding: c.1151_1152delinsG
MANE Select: NM_005957
dbSNP: rs2522873347
Type: Indel
Location: chr1:11794743 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.13 · 4 PDB

Full MTHFR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neural tube defects, folate-sensitive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MTHFR p.Leu178fs Likely pathogenic ★ same condition
MTHFR p.Glu470Leu Conflicting classifications of pathogenicity ★ same condition
MTHFR c.1166+1G>T Likely pathogenic ★★ same condition
MTHFR c.1166+5G>C Pathogenic/Likely pathogenic ★★ same condition
MTHFR c.1167-2del Pathogenic ★★ same condition
MTHFR c.1347+1G>A Pathogenic ★★ same condition
MTHFR c.1348-1G>C Likely pathogenic ★★ same condition
MTHFR c.1530+1G>A Likely 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/mthfr-p-phe384fs (accessed [today's date]).

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