Is DHFR p.Ala87= (c.261T>C) pathogenic?

DHFR p.Ala87= (c.261T>C) is classified Likely benign in DHFR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-30). Absent from gnomAD v4.1.

How common is DHFR p.Ala87= (c.261T>C) in the general population?

DHFR p.Ala87= (c.261T>C) is absent from gnomAD v4.1 (gnomAD).

DHFR p.Ala87=

c.261T>C · rs1748344765 · VCV2020414

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.5	GERP -0.056, phastCons 1
Overall
CADD	9.213	PHRED · no single calibrated threshold — expert panels disagree

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.Ala87=
Coding: c.261T>C
MANE Select: NM_000791
dbSNP: rs1748344765
Type: single nucleotide variant
Location: chr5:80637991 (GRCh38)
Gene constraint: LOEUF 0.994 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 96.32 · 89 PDB
Residue 87: the dhfr domain

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

Similar variants

DHFR p.Ala87Gly Uncertain significance ★ ⚠ same residue
DHFR p.Ala87Thr Uncertain significance ★ ⚠ same residue
DHFR c.-476C>G Likely pathogenic ★★ same type
MSH3 c.237+1G>A Likely pathogenic ★★ same type
MSH3 c.237+2T>C Pathogenic/Likely pathogenic ★★ same type
MSH3 p.Arg26Ter Pathogenic/Likely pathogenic ★★ same type
MSH3 p.Gln46Ter Pathogenic/Likely pathogenic ★★ same type
MSH3 p.Gln74Ter Pathogenic/Likely pathogenic ★★ same type

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-ala87 (accessed [today's date]).

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