Is ELF5 p.Arg57His (c.170G>A) pathogenic?

ELF5 p.Arg57His (c.170G>A) is classified Uncertain significance in ELF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-15). AlphaMissense: likely benign (0.0765); Ultra-rare (popmax 0.0307%, afr).

How common is ELF5 p.Arg57His (c.170G>A) in the general population?

ELF5 p.Arg57His (c.170G>A) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

What do computational predictors say about ELF5 p.Arg57His (c.170G>A)?

AlphaMissense predicts likely benign (score 0.0765) — an in-silico prediction, not a clinical call.

ELF5 p.Arg57His

c.170G>A · VCV4017479

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0765 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0765	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -5.69	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 2.2	GERP 0.33, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 26 kb · p 0.71 · regional, not allelic
Overall
CADD	20.3	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 R67H vs ClinVar R57H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% African / African-American · 23/74,932 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00242% 39/1,614,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0307%	3,258
Admixed American	0.00333%	30,001
South Asian	0.00329%	30,363
Finnishnot grpmax-eligible	0.00156%	64,008
European (non-Finnish)	0.000847%	118,004

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.Arg57His
Coding: c.170G>A
MANE Select: NM_001422
Type: single nucleotide variant
Location: chr11:34493664 (GRCh38)
Gene constraint: LOEUF 1.064 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.88 · 1 PDB
Residue 57: the pnt domain

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

Similar variants

ELF5 p.Arg57Cys Uncertain significance ★ ⚠ same residue
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

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-arg57his (accessed [today's date]).

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