Is ERF p.Ser24Ala (c.70T>G) pathogenic?

ERF p.Ser24Ala (c.70T>G) is classified Uncertain significance in ERF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-26). AlphaMissense: likely pathogenic (0.854); Absent from gnomAD v4.1; Associated with ERF-related disorder.

What condition is associated with ERF p.Ser24Ala (c.70T>G)?

ERF p.Ser24Ala (c.70T>G) is associated with ERF-related disorder (ClinVar).

How common is ERF p.Ser24Ala (c.70T>G) in the general population?

ERF p.Ser24Ala (c.70T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERF p.Ser24Ala (c.70T>G)?

AlphaMissense predicts likely pathogenic (score 0.854) — an in-silico prediction, not a clinical call.

ERF p.Ser24Ala

c.70T>G · rs2513525878 · VCV2632995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.854 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ERF-related disorder

Computational evidence

Protein change
AlphaMissense	0.854	likely pathogenic
REVEL	0.182	moderately benign-leaning
SaProt	LLR -10.66	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.84, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 4,550 bp · p 0.0025 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

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.Ser24Ala
Coding: c.70T>G
MANE Select: NM_006494
dbSNP: rs2513525878
Type: single nucleotide variant
Location: chr19:42250518 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.46 · 2 PDB
Residue 24: a modified residue (phosphoserine); an α-helix

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

Disease context

ERF-related disorder

Similar variants

ERF p.Ser24Ter Pathogenic/Likely pathogenic ★★ same residue
ERF p.Arg207Ter Pathogenic/Likely pathogenic ★★ same condition
ERF p.Arg218Ter Pathogenic/Likely pathogenic ★★ same condition
ERF p.Arg233Ter Pathogenic ★★ same condition
ERF p.Arg86Cys Pathogenic/Likely pathogenic ★★ same condition
ERF p.Gly53Arg Likely pathogenic ★★ same condition
ERF p.Tyr89Cys Pathogenic ★★ same condition
ERF p.Glu35Ter Pathogenic ★ 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-ser24ala (accessed [today's date]).

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