Is ELF5 p.Val5Glu (c.14T>A) pathogenic?

ELF5 p.Val5Glu (c.14T>A) is classified Uncertain significance in ELF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: ambiguous (0.4857); Very rare (popmax 0.00133%, afr).

How common is ELF5 p.Val5Glu (c.14T>A) in the general population?

ELF5 p.Val5Glu (c.14T>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ELF5 p.Val5Glu (c.14T>A)?

AlphaMissense predicts ambiguous (score 0.4857) — an in-silico prediction, not a clinical call.

ELF5 p.Val5Glu

c.14T>A · rs748736492 · VCV2485220

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4857 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4857	ambiguous
REVEL	0.237	benign-leaning
SaProt	LLR -5.72	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 26 kb · p 0.71 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V15E vs ClinVar V5E) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,928 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,640 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,928
European (non-Finnish)	0.000254%	393,275

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: ELF5
Protein: p.Val5Glu
Coding: c.14T>A
MANE Select: NM_001422
dbSNP: rs748736492
Type: single nucleotide variant
Location: chr11:34505736 (GRCh38)
Gene constraint: LOEUF 1.064 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.88 · 1 PDB

Full ELF5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELF5 p.Ala100Ser Uncertain significance ★ ⚠ same type
ELF5 p.Ala126Thr Uncertain significance ★ ⚠ same type
ELF5 p.Ala137Val Uncertain significance ★ ⚠ same type
ELF5 p.Arg116Cys Uncertain significance ★ ⚠ same type
ELF5 p.Arg116His Uncertain significance ★ ⚠ same type
ELF5 p.Arg116Leu Uncertain significance ★ ⚠ same type
ELF5 p.Arg234Gln Uncertain significance ★ ⚠ same type
ELF5 p.Arg234Trp 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/elf5-p-val5glu (accessed [today's date]).

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