Is ELP4 p.Ile313Val (c.937A>G) pathogenic?

ELP4 p.Ile313Val (c.937A>G) is classified Likely benign in ELP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: likely benign (0.0581); Very rare (popmax 0.00426%, nfe).

How common is ELP4 p.Ile313Val (c.937A>G) in the general population?

ELP4 p.Ile313Val (c.937A>G) is very rare (popmax 0.00426%, nfe) (gnomAD).

What do computational predictors say about ELP4 p.Ile313Val (c.937A>G)?

AlphaMissense predicts likely benign (score 0.0581) — an in-silico prediction, not a clinical call.

ELP4 p.Ile313Val

c.937A>G · VCV4248529

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0581 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00426%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0581	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -5.59	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 -1.7	GERP -5.6
Regional constraint	o/e 1.01	unconstrained · MANE · 274 kb · p 0.85 · regional, not allelic
Overall
CADD	0.002	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 0.00426% European (non-Finnish) · 50/1,173,188 alleles

Filtering AF 0.00328% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.0033% 53/1,605,382 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00426%	23,464
Finnishnot grpmax-eligible	0.00313%	31,969
African / African-American	0.00134%	74,554

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: ELP4
Protein: p.Ile313Val
Coding: c.937A>G
MANE Select: NM_019040
Type: single nucleotide variant
Location: chr11:31647750 (GRCh38)
Gene constraint: LOEUF 1.377 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.49

Full ELP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PAX6 p.Arg222Trp Pathogenic/Likely pathogenic ★★ same type
PAX6 p.Ter437Gln Pathogenic/Likely pathogenic ★★ same type
PAX6 p.Ter437Leu Pathogenic/Likely pathogenic ★★ same type
ELP4 p.Arg163His Uncertain significance ★★ ⚠ same type
ELP4 p.Arg31Ser Uncertain significance ★★ ⚠ same type
ELP4 p.Arg395His Uncertain significance ★★ ⚠ same type
ELP4 p.Asn244Ser Uncertain significance ★★ ⚠ same type
ELP4 p.Gln165Pro 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/elp4-p-ile313val (accessed [today's date]).

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