Is ERF p.Pro262Leu (c.785C>T) pathogenic?

ERF p.Pro262Leu (c.785C>T) is classified Likely benign in ERF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-06). AlphaMissense: likely benign (0.2814); Very rare (popmax 0.00791%, sas); Associated with Inborn genetic diseases.

What condition is associated with ERF p.Pro262Leu (c.785C>T)?

ERF p.Pro262Leu (c.785C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ERF p.Pro262Leu (c.785C>T) in the general population?

ERF p.Pro262Leu (c.785C>T) is very rare (popmax 0.00791%, sas) (gnomAD).

What do computational predictors say about ERF p.Pro262Leu (c.785C>T)?

AlphaMissense predicts likely benign (score 0.2814) — an in-silico prediction, not a clinical call.

ERF p.Pro262Leu

c.785C>T · rs769674715 · VCV2494349

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2814 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00791%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2814	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -6.19	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 12	GERP 0.73, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,421 bp · p 0.024 · regional, not allelic
Overall
CADD	25.1	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 0.00791% South Asian · 7/88,456 alleles

Filtering AF 0.00368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00261%

Overall 0.00265% 42/1,586,992 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00791%	12,637
East Asian	0.00683%	14,648
Remaining individualsnot grpmax-eligible	0.00326%	30,694
European (non-Finnish)	0.00248%	40,244
African / African-American	0.00134%	74,586

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.Pro262Leu
Coding: c.785C>T
MANE Select: NM_006494
dbSNP: rs769674715
Type: single nucleotide variant
Location: chr19:42249327 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERF p.Pro262fs Pathogenic ★ 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-pro262leu (accessed [today's date]).

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