Is ERF p.Lys71Thr (c.212A>C) pathogenic?

ERF p.Lys71Thr (c.212A>C) is classified Uncertain significance in ERF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-02). AlphaMissense: likely pathogenic (0.9994); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ERF p.Lys71Thr (c.212A>C)?

ERF p.Lys71Thr (c.212A>C) is associated with Inborn genetic diseases (ClinVar).

How common is ERF p.Lys71Thr (c.212A>C) in the general population?

ERF p.Lys71Thr (c.212A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERF p.Lys71Thr (c.212A>C)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

ERF p.Lys71Thr

c.212A>C · rs2513525561 · VCV2332302

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic · top 5% in ERF
REVEL	0.829	moderately pathogenic-leaning
SaProt	LLR -16.49	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.1	GERP 1.8, phastCons 1
Regional constraint	o/e 0.22	constrained · MANE · 558 bp · p 2.8e-12 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: ERF
Protein: p.Lys71Thr
Coding: c.212A>C
MANE Select: NM_006494
dbSNP: rs2513525561
Type: single nucleotide variant
Location: chr19:42250376 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.46 · 2 PDB
Residue 71: a DNA-binding region

Full ERF 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

ERF p.Lys71Asn Uncertain significance ★ ⚠ same residue
ERF p.Gln263Ter Pathogenic ★★ same condition
ERF p.Ala462Pro Uncertain significance ★★ ⚠ same condition
ERF p.Arg179His Uncertain significance ★★ ⚠ same condition
ERF p.Arg233Gln Uncertain significance ★★ ⚠ same condition
ERF p.Arg312Gln Uncertain significance ★★ ⚠ same condition
ERF p.Arg546Ter Uncertain significance ★★ same condition
ERF p.Lys401Glu 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/erf-p-lys71thr (accessed [today's date]).

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