Is DHFR p.Val113Phe (c.337G>T) pathogenic?

DHFR p.Val113Phe (c.337G>T) is classified Uncertain significance in DHFR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). AlphaMissense: ambiguous (0.3611); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DHFR p.Val113Phe (c.337G>T)?

DHFR p.Val113Phe (c.337G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DHFR p.Val113Phe (c.337G>T) in the general population?

DHFR p.Val113Phe (c.337G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHFR p.Val113Phe (c.337G>T)?

AlphaMissense predicts ambiguous (score 0.3611) — an in-silico prediction, not a clinical call.

DHFR p.Val113Phe

c.337G>T · VCV4011262

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3611 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3611	ambiguous
REVEL	0.669	pathogenic-leaning
SaProt	LLR -11.15	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP -1.5, phastCons 0.99
Regional constraint	o/e 0.47	unconstrained · MANE · 8,842 bp · p 2.6e-07 · regional, not allelic
Overall
CADD	21.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DHFR
Protein: p.Val113Phe
Coding: c.337G>T
MANE Select: NM_000791
Type: single nucleotide variant
Location: chr5:80637915 (GRCh38)
Gene constraint: LOEUF 0.994 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 96.32 · 89 PDB
Residue 113: the dhfr domain; a β-strand

Full DHFR 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

DHFR p.Asn30Lys Uncertain significance ★★ ⚠ same condition
DHFR p.Asn65Ser Uncertain significance ★★ ⚠ same condition
DHFR p.Pro104Ala Uncertain significance ★★ ⚠ same condition
DHFR p.Asp153His Uncertain significance ★ ⚠ same condition
DHFR p.Glu184Val Uncertain significance ★ ⚠ same condition
DHFR p.Gly21Arg Uncertain significance ★ ⚠ same condition
DHFR p.Pro27Ser Uncertain significance ★ ⚠ same condition
DHFR p.Thr40Ile 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/dhfr-p-val113phe (accessed [today's date]).

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