Is ERF p.Pro247Thr (c.739C>A) pathogenic?

ERF p.Pro247Thr (c.739C>A) is classified Uncertain significance in ERF (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-22). AlphaMissense: likely pathogenic (0.7156); Very rare (popmax 0.000172%, nfe).

How common is ERF p.Pro247Thr (c.739C>A) in the general population?

ERF p.Pro247Thr (c.739C>A) is very rare (popmax 0.000172%, nfe) (gnomAD).

What do computational predictors say about ERF p.Pro247Thr (c.739C>A)?

AlphaMissense predicts likely pathogenic (score 0.7156) — an in-silico prediction, not a clinical call.

ERF p.Pro247Thr

c.739C>A · rs371883298 · VCV1311348

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7156 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000172%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7156	likely pathogenic
REVEL	0.3	indeterminate
SaProt	LLR -8.46	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,421 bp · p 0.024 · regional, not allelic
Overall
CADD	28.0	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

Grpmax group 0.000172% European (non-Finnish) · 2/1,161,584 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00014% 2/1,423,832 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: ERF
Protein: p.Pro247Thr
Coding: c.739C>A
MANE Select: NM_006494
dbSNP: rs371883298
Type: single nucleotide variant
Location: chr19:42249373 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.46 · 2 PDB

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

Similar variants

ERF p.Arg183Ter Pathogenic ★★ same type
ERF p.Arg207Ter Pathogenic/Likely pathogenic ★★ same type
ERF p.Arg218Ter Pathogenic/Likely pathogenic ★★ same type
ERF p.Arg233Ter Pathogenic ★★ same type
ERF p.Arg86Cys Pathogenic/Likely pathogenic ★★ same type
ERF p.Gln263Ter Pathogenic ★★ same type
ERF p.Gly53Arg Likely pathogenic ★★ same type
ERF p.Ser24Ter Pathogenic/Likely pathogenic ★★ 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/erf-p-pro247thr (accessed [today's date]).

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