Is ELF5 p.Asp18Asn (c.52G>A) pathogenic?

ELF5 p.Asp18Asn (c.52G>A) is classified Uncertain significance in ELF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-11). AlphaMissense: likely benign (0.1485); Ultra-rare (popmax 0.0497%, nfe).

How common is ELF5 p.Asp18Asn (c.52G>A) in the general population?

ELF5 p.Asp18Asn (c.52G>A) is ultra-rare (popmax 0.0497%, nfe) (gnomAD).

What do computational predictors say about ELF5 p.Asp18Asn (c.52G>A)?

AlphaMissense predicts likely benign (score 0.1485) — an in-silico prediction, not a clinical call.

ELF5 p.Asp18Asn

c.52G>A · rs199968646 · VCV2532909

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1485 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0497%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1485	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -7.02	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 7.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 26 kb · p 0.71 · regional, not allelic
Overall
CADD	24.6	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D28N vs ClinVar D18N) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0497% European (non-Finnish) · 586/1,179,992 alleles

Filtering AF 0.0463% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0449%

Overall 0.0404% 652/1,613,934 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.064%	1,561
European (non-Finnish)grpmax	0.0497%	2,014
Remaining individualsnot grpmax-eligible	0.0208%	4,806
African / African-American	0.0107%	9,364
South Asian	0.00329%	30,355
Admixed American	0.00167%	59,988

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp18Asn
Coding: c.52G>A
MANE Select: NM_001422
dbSNP: rs199968646
Type: single nucleotide variant
Location: chr11:34505698 (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-asp18asn (accessed [today's date]).

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