Is ERRFI1 p.Lys336Arg (c.1007A>G) pathogenic?

ERRFI1 p.Lys336Arg (c.1007A>G) is classified Uncertain significance in ERRFI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.1728); Very rare (popmax 8.47e-05%, nfe).

How common is ERRFI1 p.Lys336Arg (c.1007A>G) in the general population?

ERRFI1 p.Lys336Arg (c.1007A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ERRFI1 p.Lys336Arg (c.1007A>G)?

AlphaMissense predicts likely benign (score 0.1728) — an in-silico prediction, not a clinical call.

ERRFI1 p.Lys336Arg

c.1007A>G · VCV4250974

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1728 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1728	likely benign
REVEL	0.23	benign-leaning
SaProt	LLR -5.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 2,406 bp · p 0.00016 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,022 alleles

Overall 6.84e-05% 1/1,461,866 alleles · very rare

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: ERRFI1
Protein: p.Lys336Arg
Coding: c.1007A>G
MANE Select: NM_018948
Type: single nucleotide variant
Location: chr1:8013592 (GRCh38)
Gene constraint: LOEUF 1.088 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.20 · 7 PDB
Residue 336: the 'disordered' region; the 'interaction with egfr and erbb2 and regulation of egfr activation' region

Full ERRFI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERRFI1 p.Arg244= Benign ★★ same type
ERRFI1 p.Ile158Leu Benign ★★ same type
ERRFI1 p.Pro239Leu Benign ★★ same type
ERRFI1 p.Ala4Val Uncertain significance ★ ⚠ same type
ERRFI1 p.Ala8Thr Uncertain significance ★ ⚠ same type
ERRFI1 p.Arg148Trp Uncertain significance ★ ⚠ same type
ERRFI1 p.Arg245Lys Uncertain significance ★ ⚠ same type
ERRFI1 p.Arg331Cys 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/errfi1-p-lys336arg (accessed [today's date]).

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