Is ELFN2 p.Asn76Ser (c.227A>G) pathogenic?

ELFN2 p.Asn76Ser (c.227A>G) is classified Benign in ELFN2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-07-26). AlphaMissense: likely benign (0.0506); Rare (popmax 0.957%, afr).

How common is ELFN2 p.Asn76Ser (c.227A>G) in the general population?

ELFN2 p.Asn76Ser (c.227A>G) is rare (popmax 0.957%, afr) (gnomAD).

What do computational predictors say about ELFN2 p.Asn76Ser (c.227A>G)?

AlphaMissense predicts likely benign (score 0.0506) — an in-silico prediction, not a clinical call.

ELFN2 p.Asn76Ser

c.227A>G · rs151050985 · VCV786382

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0506 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.957%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0506	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -4.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.16	GERP 1.1, phastCons 0.99
Regional constraint	o/e 0.66	unconstrained · MANE · 1,131 bp · p 4.2e-15 · regional, not allelic
Overall
CADD	9.729	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 0.957% African / African-American · 717/74,924 alleles

Filtering AF 0.899% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.876%

Overall 0.0487% 786/1,613,940 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.957%	104
Remaining individualsnot grpmax-eligible	0.0528%	1,894
Admixed American	0.04%	2,500
Middle Eastern	0.033%	3,031
South Asian	0.00329%	30,354
East Asian	0.00223%	44,870
European (non-Finnish)	0.000508%	196,666

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.Asn76Ser
Coding: c.227A>G
MANE Select: NM_052906
dbSNP: rs151050985
Type: single nucleotide variant
Location: chr22:37375308 (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.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
ELFN2 p.Ala560Val 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-asn76ser (accessed [today's date]).

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