Is EPO p.Arg177Gln (c.530G>A) pathogenic?

EPO p.Arg177Gln (c.530G>A) is classified Pathogenic in EPO (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-06-23). AlphaMissense: likely benign (0.175); Very rare (popmax 0.00167%, amr); Associated with Diamond-Blackfan anemia-like.

What condition is associated with EPO p.Arg177Gln (c.530G>A)?

EPO p.Arg177Gln (c.530G>A) is associated with Diamond-Blackfan anemia-like (ClinVar).

How common is EPO p.Arg177Gln (c.530G>A) in the general population?

EPO p.Arg177Gln (c.530G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about EPO p.Arg177Gln (c.530G>A)?

AlphaMissense predicts likely benign (score 0.175) — an in-silico prediction, not a clinical call.

EPO p.Arg177Gln

c.530G>A · rs1358275550 · VCV496595

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.175 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Diamond-Blackfan anemia-like

Computational evidence

Protein change
AlphaMissense	0.175	likely benign ⚠ discordant with ClinVar
REVEL	0.351	indeterminate
SaProt	LLR -6.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.2, phastCons 1
Overall
CADD	26.8	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 0.00167% Admixed American · 1/59,960 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,613,920 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,960
European (non-Finnish)	0.000424%	236,005

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: EPO
Protein: p.Arg177Gln
Coding: c.530G>A
MANE Select: NM_003254 · reported on NM_000799
dbSNP: rs1358275550
Type: single nucleotide variant
Location: chr7:100723081 (GRCh38)
Structure: AlphaFold pLDDT 90.09 · 13 PDB
Residue 177: a disulfide bond; a β-strand

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

Disease context

Diamond-Blackfan anemia-like — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EPO c.14-1G>C Uncertain significance ★★ same type
EPO c.13+10C>T Benign/Likely benign ★★ same type
EPO c.247-66G>A Benign ★★ same type
EPO p.Ala151= Benign ★★ same type
EPO p.Ala57= Likely benign ★★ same type
EPO p.Ala87= Likely benign ★★ same type
EPO p.Asp70Asn Likely benign ★★ same type
EPO p.Lys79= Benign/Likely benign ★★ 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/epo-p-arg177gln (accessed [today's date]).

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