Is ERRFI1 p.Ala8Thr (c.22G>A) pathogenic?

ERRFI1 p.Ala8Thr (c.22G>A) is classified Uncertain significance in ERRFI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-27). AlphaMissense: likely benign (0.1458); Absent from gnomAD v4.1.

How common is ERRFI1 p.Ala8Thr (c.22G>A) in the general population?

ERRFI1 p.Ala8Thr (c.22G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERRFI1 p.Ala8Thr (c.22G>A)?

AlphaMissense predicts likely benign (score 0.1458) — an in-silico prediction, not a clinical call.

ERRFI1 p.Ala8Thr

c.22G>A · VCV3846179

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1458 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1458	likely benign
REVEL	0.259	benign-leaning
SaProt	LLR -6.36	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 5.9	GERP 2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 2,406 bp · p 0.00016 · regional, not allelic
Overall
CADD	24.3	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

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: ERRFI1
Protein: p.Ala8Thr
Coding: c.22G>A
MANE Select: NM_018948
Type: single nucleotide variant
Location: chr1:8015598 (GRCh38)
Gene constraint: LOEUF 1.088 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.20 · 7 PDB

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.Arg148Trp Uncertain significance ★ ⚠ same type
ERRFI1 p.Arg245Lys Uncertain significance ★ ⚠ same type
ERRFI1 p.Arg331Cys Uncertain significance ★ same type
ERRFI1 p.Arg37Leu 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-ala8thr (accessed [today's date]).

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