Is ELFN1 p.Arg236His (c.707G>A) pathogenic?

ELFN1 p.Arg236His (c.707G>A) is classified Uncertain significance in ELFN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-12). AlphaMissense: likely benign (0.0799); Ultra-rare (popmax 0.0269%, eas).

How common is ELFN1 p.Arg236His (c.707G>A) in the general population?

ELFN1 p.Arg236His (c.707G>A) is ultra-rare (popmax 0.0269%, eas) (gnomAD).

What do computational predictors say about ELFN1 p.Arg236His (c.707G>A)?

AlphaMissense predicts likely benign (score 0.0799) — an in-silico prediction, not a clinical call.

ELFN1 p.Arg236His

c.707G>A · rs887624907 · VCV2599976

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0799 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0269%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.0799	likely benign
SaProt	LLR -7.13	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 3.2	GERP 1.4, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 738 bp · p 3.5e-08 · regional, not allelic
Overall
CADD	21.9	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 0.0269% East Asian · 11/40,910 alleles

Filtering AF 0.0151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0116%

Overall 0.00357% 55/1,538,540 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0269%	3,719
African / African-American	0.00411%	24,349
Admixed American	0.00392%	25,490
Remaining individualsnot grpmax-eligible	0.00333%	29,997
European (non-Finnish)	0.00305%	32,766
Finnishnot grpmax-eligible	0.00212%	47,186
South Asian	0.00119%	84,058

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.Arg236His
Coding: c.707G>A
MANE Select: NM_001128636
dbSNP: rs887624907
Type: single nucleotide variant
Location: chr7:1745303 (GRCh38)
Gene constraint: LOEUF 1.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 5 PDB
Residue 236: the lrrct domain

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-arg236his (accessed [today's date]).

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