Is RPS7 p.Val9Met (c.25G>A) pathogenic?

RPS7 p.Val9Met (c.25G>A) is classified Uncertain significance in RPS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-06). AlphaMissense: ambiguous (0.3667); Very rare (popmax 0.004%, afr); Associated with Diamond-Blackfan anemia 8.

What condition is associated with RPS7 p.Val9Met (c.25G>A)?

RPS7 p.Val9Met (c.25G>A) is associated with Diamond-Blackfan anemia 8 (ClinVar).

How common is RPS7 p.Val9Met (c.25G>A) in the general population?

RPS7 p.Val9Met (c.25G>A) is very rare (popmax 0.004%, afr) (gnomAD).

How is Diamond-Blackfan anemia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about RPS7 p.Val9Met (c.25G>A)?

AlphaMissense predicts ambiguous (score 0.3667) — an in-silico prediction, not a clinical call.

RPS7 p.Val9Met

c.25G>A · VCV3586567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3667 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Diamond-Blackfan anemia 8

Computational evidence

Protein change
AlphaMissense	0.3667	ambiguous
REVEL	0.157	moderately benign-leaning
SaProt	LLR -12.60	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 907 bp · p 0.17 · regional, not allelic
Overall
CADD	24.7	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 0.004% African / African-American · 3/74,976 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000206% 3/1,459,014 alleles · very rare

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: RPS7
Protein: p.Val9Met
Coding: c.25G>A
MANE Select: NM_001011
Type: single nucleotide variant
Location: chr2:3575634 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 87.04 · 182 PDB
Residue 9: an α-helix

Full RPS7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Diamond-Blackfan anemia 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Diamond-Blackfan anemia (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

RPS7 c.75+1G>A Pathogenic ★★ same condition
RPS7 c.356+6T>C Uncertain significance ★★ same condition
RPS7 c.-27C>T Uncertain significance ★★ same condition
RPS7 p.Ala26Val Uncertain significance ★★ ⚠ same condition
RPS7 p.Ala38Val Uncertain significance ★★ ⚠ same condition
RPS7 p.Arg145His Uncertain significance ★★ ⚠ same condition
RPS7 p.Arg152Pro Uncertain significance ★★ ⚠ same condition
RPS7 p.Asn12Ser Uncertain significance ★★ ⚠ same condition

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/rps7-p-val9met (accessed [today's date]).

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