Is ELL p.Arg314His (c.941G>A) pathogenic?

ELL p.Arg314His (c.941G>A) is classified Likely benign in ELL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.0555); Very rare (popmax 0.00512%, sas).

How common is ELL p.Arg314His (c.941G>A) in the general population?

ELL p.Arg314His (c.941G>A) is very rare (popmax 0.00512%, sas) (gnomAD).

What do computational predictors say about ELL p.Arg314His (c.941G>A)?

AlphaMissense predicts likely benign (score 0.0555) — an in-silico prediction, not a clinical call.

ELL p.Arg314His

c.941G>A · VCV4248321

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0555 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00512%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0555	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -7.71	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 -0.29	GERP -2.4
Regional constraint	o/e 0.92	unconstrained · MANE · 77 kb · p 0.013 · regional, not allelic
Overall
CADD	8.394	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 0.00512% South Asian · 4/78,162 alleles

Filtering AF 0.00169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00101%

Overall 0.00154% 23/1,493,654 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00512%	19,540
European (non-Finnish)	0.00168%	59,467

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: ELL
Protein: p.Arg314His
Coding: c.941G>A
MANE Select: NM_006532
Type: single nucleotide variant
Location: chr19:18451577 (GRCh38)
Gene constraint: LOEUF 0.466 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.31 · 1 PDB
Residue 314: the 'disordered' region

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

Similar variants

ELL p.Arg314Cys Uncertain significance ★ ⚠ same residue
ELL p.Leu427= Benign ★★ same type
ELL p.Ser297Asn Benign ★★ same type
ELL p.Ala172Val Uncertain significance ★ ⚠ same type
ELL p.Ala237Gly Uncertain significance ★ ⚠ same type
ELL p.Ala237Val Uncertain significance ★ ⚠ same type
ELL p.Ala241Val Uncertain significance ★ ⚠ same type
ELL p.Ala348Val 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/ell-p-arg314his (accessed [today's date]).

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