Is ELFN2 p.Phe406Val (c.1216T>G) pathogenic?

ELFN2 p.Phe406Val (c.1216T>G) is classified Uncertain significance in ELFN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: ambiguous (0.5216); Very rare (popmax 0.00891%, eas).

How common is ELFN2 p.Phe406Val (c.1216T>G) in the general population?

ELFN2 p.Phe406Val (c.1216T>G) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about ELFN2 p.Phe406Val (c.1216T>G)?

AlphaMissense predicts ambiguous (score 0.5216) — an in-silico prediction, not a clinical call.

ELFN2 p.Phe406Val

c.1216T>G · rs768664794 · VCV3088274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5216 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Computational evidence

Protein change
AlphaMissense	0.5216	ambiguous
REVEL	0.433	indeterminate
SaProt	LLR -5.49	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,327 bp · p 0.0019 · regional, not allelic
Overall
CADD	26.4	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 0.00891% East Asian · 4/44,880 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000248% 4/1,613,802 alleles · very rare

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: ELFN2
Protein: p.Phe406Val
Coding: c.1216T>G
MANE Select: NM_052906
dbSNP: rs768664794
Type: single nucleotide variant
Location: chr22:37374319 (GRCh38)
Gene constraint: LOEUF 0.566 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 61.79

Full ELFN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELFN2 p.Asn76Ser Benign ★★ same type
ELFN2 p.Ser262Tyr Benign ★★ same type
ELFN2 p.Ala183Thr Uncertain significance ★ ⚠ same type
ELFN2 p.Ala198Val Uncertain significance ★ ⚠ same type
ELFN2 p.Ala243Gly Uncertain significance ★ ⚠ same type
ELFN2 p.Ala265Thr Uncertain significance ★ ⚠ same type
ELFN2 p.Ala455Thr Uncertain significance ★ ⚠ same type
ELFN2 p.Ala484Thr Uncertain significance ★ ⚠ 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/elfn2-p-phe406val (accessed [today's date]).

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