Is ELFN2 p.Ser262Tyr (c.785C>A) pathogenic?

ELFN2 p.Ser262Tyr (c.785C>A) is classified Benign in ELFN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-26). AlphaMissense: likely benign (0.1461); Low-frequency (popmax 3.27%, afr).

How common is ELFN2 p.Ser262Tyr (c.785C>A) in the general population?

ELFN2 p.Ser262Tyr (c.785C>A) is low-frequency (popmax 3.27%, afr) (gnomAD).

What do computational predictors say about ELFN2 p.Ser262Tyr (c.785C>A)?

AlphaMissense predicts likely benign (score 0.1461) — an in-silico prediction, not a clinical call.

ELFN2 p.Ser262Tyr

c.785C>A · rs6000698 · VCV717069

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1461 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.27%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1461	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -7.45	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 12	GERP 2, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 1,131 bp · p 4.2e-15 · regional, not allelic
Overall
CADD	18.37	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 3.27% African / African-American · 2,451/75,038 alleles

Filtering AF 3.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.11%

Overall 0.177% 2,847/1,610,996 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.27%	31
Middle Eastern	0.429%	233
Admixed American	0.23%	435
Remaining individualsnot grpmax-eligible	0.195%	512
European (non-Finnish)	0.00899%	11,125
South Asian	0.00439%	22,761

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.Ser262Tyr
Coding: c.785C>A
MANE Select: NM_052906
dbSNP: rs6000698
Type: single nucleotide variant
Location: chr22:37374750 (GRCh38)
Gene constraint: LOEUF 0.566 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 61.79
Residue 262: the 'disordered' region

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

Similar variants

ELFN2 p.Ser262Pro Uncertain significance ★ ⚠ same residue
ELFN2 p.Asn76Ser 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-ser262tyr (accessed [today's date]).

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