Is ELF2 p.Ile438Val (c.1312A>G) pathogenic?

ELF2 p.Ile438Val (c.1312A>G) is classified Uncertain significance in ELF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-19). AlphaMissense: likely benign (0.1309); Very rare (popmax 0.00333%, amr).

How common is ELF2 p.Ile438Val (c.1312A>G) in the general population?

ELF2 p.Ile438Val (c.1312A>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about ELF2 p.Ile438Val (c.1312A>G)?

AlphaMissense predicts likely benign (score 0.1309) — an in-silico prediction, not a clinical call.

ELF2 p.Ile438Val

c.1312A>G · VCV3507848

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1309 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1309	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -6.39	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 6.2	GERP 2, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 1,626 bp · p 8.7e-05 · regional, not allelic
Overall
CADD	18.61	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 0.00333% Admixed American · 2/59,990 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00217% 35/1,613,866 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0141%	7,115
Admixed Americangrpmax	0.00333%	29,995
South Asian	0.0022%	45,537
European (non-Finnish)	0.00186%	53,630

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ELF2
Protein: p.Ile438Val
Coding: c.1312A>G
MANE Select: NM_001331036
Type: single nucleotide variant
Location: chr4:139059453 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.58 · 1 PDB

Full ELF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELF2 p.Ile438Met Uncertain significance ★ ⚠ same residue
ELF2 p.Ala4Thr Likely pathogenic ★ ⚠ same type
ELF2 p.Ala135Pro Uncertain significance ★ ⚠ same type
ELF2 p.Ala368Val Uncertain significance ★ ⚠ same type
ELF2 p.Ala383Val Uncertain significance ★ ⚠ same type
ELF2 p.Ala428Val Uncertain significance ★ ⚠ same type
ELF2 p.Ala444Gly Uncertain significance ★ ⚠ same type
ELF2 p.Ala517Ser 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/elf2-p-ile438val (accessed [today's date]).

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