Is ELFN1 p.Arg121His (c.362G>A) pathogenic?

ELFN1 p.Arg121His (c.362G>A) is classified Uncertain significance in ELFN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-05). AlphaMissense: likely benign (0.1779); Very rare (popmax 0.00784%, amr).

How common is ELFN1 p.Arg121His (c.362G>A) in the general population?

ELFN1 p.Arg121His (c.362G>A) is very rare (popmax 0.00784%, amr) (gnomAD).

What do computational predictors say about ELFN1 p.Arg121His (c.362G>A)?

AlphaMissense predicts likely benign (score 0.1779) — an in-silico prediction, not a clinical call.

ELFN1 p.Arg121His

c.362G>A · VCV3507882

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1779 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00784%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.1779	likely benign
SaProt	LLR -8.11	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 8.4	GERP 0.41, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 738 bp · p 3.5e-08 · regional, not allelic
Overall
CADD	24.1	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 0.00784% Admixed American · 4/51,002 alleles

Filtering AF 0.00422% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00382%

Overall 0.00471% 73/1,551,190 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00784%	12,750
European (non-Finnish)	0.00532%	18,804
Remaining individualsnot grpmax-eligible	0.00499%	20,035
East Asian	0.00244%	40,926
South Asian	0.00238%	42,036
Finnishnot grpmax-eligible	0.00168%	59,392
African / African-American	0.00137%	73,046

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.Arg121His
Coding: c.362G>A
MANE Select: NM_001128636
Type: single nucleotide variant
Location: chr7:1744958 (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-arg121his (accessed [today's date]).

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