Is ELP2 p.Val49Ile (c.145G>A) pathogenic?

ELP2 p.Val49Ile (c.145G>A) is classified Uncertain significance in ELP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-25). AlphaMissense: likely benign (0.0757); Very rare (popmax 0.00671%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ELP2 p.Val49Ile (c.145G>A)?

ELP2 p.Val49Ile (c.145G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ELP2 p.Val49Ile (c.145G>A) in the general population?

ELP2 p.Val49Ile (c.145G>A) is very rare (popmax 0.00671%, nfe) (gnomAD).

What do computational predictors say about ELP2 p.Val49Ile (c.145G>A)?

AlphaMissense predicts likely benign (score 0.0757) — an in-silico prediction, not a clinical call.

ELP2 p.Val49Ile

c.145G>A · VCV4618459

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0757 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00671%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0757	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -3.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.8	GERP 0.47, phastCons 0.95
Regional constraint	o/e 0.95	unconstrained · MANE · 45 kb · p 0.13 · regional, not allelic
Overall
CADD	15.21	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 0.00671% European (non-Finnish) · 79/1,177,798 alleles

Filtering AF 0.00547% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00507%

Overall 0.00509% 82/1,611,396 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00671%	14,909
Admixed American	0.00333%	29,992
Remaining individualsnot grpmax-eligible	0.0016%	62,376

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: ELP2
Protein: p.Val49Ile
Coding: c.145G>A
MANE Select: NM_018255
Type: single nucleotide variant
Location: chr18:36133244 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49 · 4 PDB
Residue 49: a β-strand

Full ELP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ELP2 p.Val49Gly Uncertain significance ★ ⚠ same residue
ELP2 p.Val49= Likely benign ★ same residue
ELP2 p.Ala741Val Uncertain significance ★★ ⚠ same condition
ELP2 p.Arg468Trp Uncertain significance ★★ ⚠ same condition
ELP2 p.Asp71Gly Uncertain significance ★★ ⚠ same condition
ELP2 p.Gln606Pro Uncertain significance ★★ ⚠ same condition
ELP2 p.Val728Ile Uncertain significance ★★ ⚠ same condition
ELP2 p.Asn709Ser Likely benign ★★ same condition

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/elp2-p-val49ile (accessed [today's date]).

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