Is ERFL p.Ser265Leu (c.794C>T) pathogenic?

ERFL p.Ser265Leu (c.794C>T) is classified Likely benign in ERFL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). AlphaMissense: likely benign (0.0845); Rare (popmax 0.474%, nfe).

How common is ERFL p.Ser265Leu (c.794C>T) in the general population?

ERFL p.Ser265Leu (c.794C>T) is rare (popmax 0.474%, nfe) (gnomAD).

What do computational predictors say about ERFL p.Ser265Leu (c.794C>T)?

AlphaMissense predicts likely benign (score 0.0845) — an in-silico prediction, not a clinical call.

ERFL p.Ser265Leu

c.794C>T · VCV3388920

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0845 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.474%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.0845	likely benign
SaProt	LLR -6.52	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.5	GERP 1.1, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 1,752 bp · p 7.6e-11 · regional, not allelic
Overall
CADD	18.7	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 0.474% European (non-Finnish) · 4,687/987,938 alleles

Filtering AF 0.463% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.458%

Overall 0.402% 4,948/1,231,662 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.474%	211
Remaining individualsnot grpmax-eligible	0.282%	355
Ashkenazi Jewishnot grpmax-eligible	0.213%	470
African / African-American	0.0729%	1,373
Admixed American	0.0632%	1,582
Finnishnot grpmax-eligible	0.0568%	1,762
South Asian	0.0534%	1,871
Middle Eastern	0.0312%	3,208

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: ERFL
Protein: p.Ser265Leu
Coding: c.794C>T
MANE Select: NM_004706 · reported on NM_001365103
Type: single nucleotide variant
Location: chr19:41908499 (GRCh38)

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

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/erfl-p-ser265leu (accessed [today's date]).

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