Is ELP4 p.Ala11Thr (c.31G>A) pathogenic?

ELP4 p.Ala11Thr (c.31G>A) is classified Likely benign in ELP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-12). AlphaMissense: likely benign (0.0767); Ultra-rare (popmax 0.0134%, eas).

How common is ELP4 p.Ala11Thr (c.31G>A) in the general population?

ELP4 p.Ala11Thr (c.31G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about ELP4 p.Ala11Thr (c.31G>A)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

ELP4 p.Ala11Thr

c.31G>A · rs372209718 · VCV3088519

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -7.05	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 -3.8	GERP -2.4
Regional constraint	o/e 1.01	unconstrained · MANE · 274 kb · p 0.85 · regional, not allelic
Overall
CADD	0.124	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 0.0134% East Asian · 6/44,896 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00136% 22/1,614,024 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,483
Admixed American	0.0133%	7,502
Remaining individualsnot grpmax-eligible	0.008%	12,495
European (non-Finnish)	0.000254%	393,343

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.Ala11Thr
Coding: c.31G>A
MANE Select: NM_019040
dbSNP: rs372209718
Type: single nucleotide variant
Location: chr11:31509815 (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-ala11thr (accessed [today's date]).

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