Is EARS2 p.Arg162Gln (c.485G>A) pathogenic?

EARS2 p.Arg162Gln (c.485G>A) is classified Uncertain significance in EARS2 (ClinVar, Single submitter, 2 submitters; last evaluated 2016-08-26). AlphaMissense: likely benign (0.1372); Ultra-rare (popmax 0.0446%, eas).

How common is EARS2 p.Arg162Gln (c.485G>A) in the general population?

EARS2 p.Arg162Gln (c.485G>A) is ultra-rare (popmax 0.0446%, eas) (gnomAD).

What do computational predictors say about EARS2 p.Arg162Gln (c.485G>A)?

AlphaMissense predicts likely benign (score 0.1372) — an in-silico prediction, not a clinical call.

EARS2 p.Arg162Gln

c.485G>A · rs752779979 · VCV290961

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1372 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1372	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -10.17	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.59	donor gain · deltas
Pangolin	Δ0.26	gain · loss 0.10 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 22 kb · p 0.014 · regional, not allelic
Overall
CADD	37.0	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 0.0446% East Asian · 20/44,876 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.00186% 30/1,612,454 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0446%	2,244
Remaining individualsnot grpmax-eligible	0.00641%	15,604
Admixed American	0.00502%	19,923
South Asian	0.0022%	45,449
African / African-American	0.00133%	74,990

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: EARS2
Protein: p.Arg162Gln
Coding: c.485G>A
MANE Select: NM_001083614
dbSNP: rs752779979
Type: single nucleotide variant
Location: chr16:23544514 (GRCh38)
Gene constraint: LOEUF 1.138 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.84

Full EARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EARS2 p.Arg162Trp Uncertain significance ★★ ⚠ same residue
EARS2 p.Arg107His Pathogenic/Likely pathogenic ★★ ⚠ same type
EARS2 p.Arg108Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
EARS2 p.Cys167Tyr Pathogenic/Likely pathogenic ★★ same type
EARS2 p.Gly317Cys Pathogenic ★★ same type
EARS2 p.Met1Val Pathogenic/Likely pathogenic ★★ same type
EARS2 p.Ser143Ter Pathogenic ★★ same type
EARS2 p.Ala263Thr 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/ears2-p-arg162gln (accessed [today's date]).

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