Is ELFN1 p.Arg274Cys (c.820C>T) pathogenic?

ELFN1 p.Arg274Cys (c.820C>T) is classified Uncertain significance in ELFN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-12). AlphaMissense: likely benign (0.1675); Ultra-rare (popmax 0.0167%, mid).

How common is ELFN1 p.Arg274Cys (c.820C>T) in the general population?

ELFN1 p.Arg274Cys (c.820C>T) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about ELFN1 p.Arg274Cys (c.820C>T)?

AlphaMissense predicts likely benign (score 0.1675) — an in-silico prediction, not a clinical call.

ELFN1 p.Arg274Cys

c.820C>T · rs768568611 · VCV3088271

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1675 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.1675	likely benign
SaProt	LLR -9.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.2, phastCons 0.31
Regional constraint	o/e 1.05	unconstrained · MANE · 1,744 bp · p 0.16 · regional, not allelic
Overall
CADD	18.63	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

Grpmax group 0.0167% Middle Eastern · 1/5,998 alleles

Filtering AF 0.00383% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00248%

Overall 0.00123% 19/1,538,846 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,998
Admixed American	0.00982%	10,182
South Asian	0.00119%	83,960
European (non-Finnish)	0.00105%	95,506

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: ELFN1
Protein: p.Arg274Cys
Coding: c.820C>T
MANE Select: NM_001128636
dbSNP: rs768568611
Type: single nucleotide variant
Location: chr7:1745416 (GRCh38)
Gene constraint: LOEUF 1.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 5 PDB
Residue 274: the 'disordered' region

Full ELFN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELFN1 p.Arg274His Uncertain significance ★ ⚠ same residue
ELFN1 p.Ala14= Benign/Likely benign ★★ same type
ELFN1 p.Ala796= Benign/Likely benign ★★ same type
ELFN1 p.Asp618= Likely benign ★★ same type
ELFN1 p.Cys196= Likely benign ★★ same type
ELFN1 p.Glu258= Benign/Likely benign ★★ same type
ELFN1 p.Gly228= Benign/Likely benign ★★ same type
ELFN1 p.His20= Benign/Likely benign ★★ 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/elfn1-p-arg274cys (accessed [today's date]).

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