Is ELP2 p.Ala112Val (c.335C>T) pathogenic?

ELP2 p.Ala112Val (c.335C>T) is classified Uncertain significance in ELP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). AlphaMissense: likely benign (0.1244); Ultra-rare (popmax 0.0538%, sas); Associated with Inborn genetic diseases.

What condition is associated with ELP2 p.Ala112Val (c.335C>T)?

ELP2 p.Ala112Val (c.335C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ELP2 p.Ala112Val (c.335C>T) in the general population?

ELP2 p.Ala112Val (c.335C>T) is ultra-rare (popmax 0.0538%, sas) (gnomAD).

What do computational predictors say about ELP2 p.Ala112Val (c.335C>T)?

AlphaMissense predicts likely benign (score 0.1244) — an in-silico prediction, not a clinical call.

ELP2 p.Ala112Val

c.335C>T · rs538079080 · VCV3088507

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1244 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0538%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1244	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -8.64	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 1.4	GERP 0.065, phastCons 0.76
Regional constraint	o/e 0.95	unconstrained · MANE · 45 kb · p 0.13 · regional, not allelic
Overall
CADD	19.85	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 0.0538% South Asian · 49/91,084 alleles

Filtering AF 0.0418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0374%

Overall 0.00452% 73/1,614,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0538%	1,859
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.016%	6,250
African / African-American	0.00133%	75,030
European (non-Finnish)	0.00102%	98,327

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.Ala112Val
Coding: c.335C>T
MANE Select: NM_018255
dbSNP: rs538079080
Type: single nucleotide variant
Location: chr18:36138316 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49 · 4 PDB
Residue 112: 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.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-ala112val (accessed [today's date]).

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