Is ELP2 p.Val573Ala (c.1718T>C) pathogenic?

ELP2 p.Val573Ala (c.1718T>C) is classified Uncertain significance in ELP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-12). AlphaMissense: ambiguous (0.4138); Very rare (popmax 0.00834%, amr); Associated with Inborn genetic diseases.

What condition is associated with ELP2 p.Val573Ala (c.1718T>C)?

ELP2 p.Val573Ala (c.1718T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ELP2 p.Val573Ala (c.1718T>C) in the general population?

ELP2 p.Val573Ala (c.1718T>C) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about ELP2 p.Val573Ala (c.1718T>C)?

AlphaMissense predicts ambiguous (score 0.4138) — an in-silico prediction, not a clinical call.

ELP2 p.Val573Ala

c.1718T>C · VCV3844563

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4138 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4138	ambiguous
REVEL	0.357	indeterminate
SaProt	LLR -9.36	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 45 kb · p 0.13 · regional, not allelic
Overall
CADD	26.5	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 0.00834% Admixed American · 5/59,982 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00031% 5/1,613,578 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: ELP2
Protein: p.Val573Ala
Coding: c.1718T>C
MANE Select: NM_018255
Type: single nucleotide variant
Location: chr18:36160961 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49 · 4 PDB

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.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
ELP2 p.Glu263Gly Likely benign ★★ ⚠ same condition
ELP2 p.Tyr439Cys 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-val573ala (accessed [today's date]).

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