Is NFE2L2 p.Phe71= (c.213C>T) pathogenic?

NFE2L2 p.Phe71= (c.213C>T) is classified Likely benign in NFE2L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). Very rare (popmax 0.00333%, amr).

How common is NFE2L2 p.Phe71= (c.213C>T) in the general population?

NFE2L2 p.Phe71= (c.213C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

NFE2L2 p.Phe71=

c.213C>T · rs775813661 · VCV2978489

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 -6	GERP -4
Overall
CADD	2.836	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,002 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00217% 35/1,613,982 alleles · very rare exomes 33/1,461,878 · genomes 2/152,104 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,001
European (non-Finnish)	0.00263%	38,065
Remaining individualsnot grpmax-eligible	0.0016%	62,486
Finnishnot grpmax-eligible	0.00156%	63,994

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: NFE2L2
Protein: p.Phe71=
Coding: c.213C>T
MANE Select: NM_006164
dbSNP: rs775813661
Type: single nucleotide variant
Location: chr2:177234104 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 61.72 · 23 PDB

Full NFE2L2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NFE2L2 p.Ala249Ser Uncertain significance ★★ ⚠ same type
NFE2L2 p.Ala496Gly Uncertain significance ★★ ⚠ same type
NFE2L2 p.Arg34Gln Uncertain significance ★★ ⚠ same type
NFE2L2 p.Arg449Cys Uncertain significance ★★ ⚠ same type
NFE2L2 p.Arg569Cys Uncertain significance ★★ ⚠ same type
NFE2L2 p.Asn101Ser Uncertain significance ★★ ⚠ same type
NFE2L2 p.Asn225Ser Uncertain significance ★★ ⚠ same type
NFE2L2 p.Asn278Ser Uncertain significance ★★ ⚠ 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/nfe2l2-p-phe71 (accessed [today's date]).

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