Is ELFN1 p.Arg779Cys (c.2335C>T) pathogenic?

ELFN1 p.Arg779Cys (c.2335C>T) is classified Uncertain significance in ELFN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-07). AlphaMissense: ambiguous (0.513); Very rare (popmax 0.00245%, eas).

How common is ELFN1 p.Arg779Cys (c.2335C>T) in the general population?

ELFN1 p.Arg779Cys (c.2335C>T) is very rare (popmax 0.00245%, eas) (gnomAD).

What do computational predictors say about ELFN1 p.Arg779Cys (c.2335C>T)?

AlphaMissense predicts ambiguous (score 0.513) — an in-silico prediction, not a clinical call.

ELFN1 p.Arg779Cys

c.2335C>T · VCV3507877

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.513 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00245%, eas)

Computational evidence

Protein change
AlphaMissense	0.513	ambiguous
SaProt	LLR -10.68	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.5, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,744 bp · p 0.16 · regional, not allelic
Overall
CADD	32.0	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 0.00245% East Asian · 1/40,876 alleles

Filtering AF 0.000515% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000376%

Overall 0.00114% 16/1,397,444 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00245%	40,876
South Asian	0.00239%	41,833
Admixed American	0.00197%	50,880
Finnishnot grpmax-eligible	0.0017%	58,826
European (non-Finnish)	0.000959%	104,240

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.Arg779Cys
Coding: c.2335C>T
MANE Select: NM_001128636
Type: single nucleotide variant
Location: chr7:1746931 (GRCh38)
Gene constraint: LOEUF 1.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 5 PDB

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

Similar variants

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
ELFN1 p.Pro614= 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-arg779cys (accessed [today's date]).

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