Is GATA1 p.Ser36Phe (c.107C>T) pathogenic?

GATA1 p.Ser36Phe (c.107C>T) is classified Uncertain significance in GATA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-30). AlphaMissense: likely benign (0.251); Very rare (popmax 0.000112%, nfe); Associated with Diamond-Blackfan anemia.

What condition is associated with GATA1 p.Ser36Phe (c.107C>T)?

GATA1 p.Ser36Phe (c.107C>T) is associated with Diamond-Blackfan anemia, GATA1-related cytopenia (ClinVar).

How common is GATA1 p.Ser36Phe (c.107C>T) in the general population?

GATA1 p.Ser36Phe (c.107C>T) is very rare (popmax 0.000112%, nfe) (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 GATA1 p.Ser36Phe (c.107C>T)?

AlphaMissense predicts likely benign (score 0.251) — an in-silico prediction, not a clinical call.

GATA1 p.Ser36Phe

c.107C>T · rs782155672 · VCV2946049

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.251 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Diamond-Blackfan anemia

Computational evidence

Protein change
AlphaMissense	0.251	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -7.67	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 6.9	GERP 1.3, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 1,213 bp · p 0.41 · regional, not allelic
Overall
CADD	22.9	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/892,488 alleles

Overall 9.16e-05% 1/1,092,284 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: GATA1
Protein: p.Ser36Phe
Coding: c.107C>T
MANE Select: NM_002049
dbSNP: rs782155672
Type: single nucleotide variant
Location: chrX:48791216 (GRCh38)
Structure: AlphaFold pLDDT 59.48 · 1 PDB

Full GATA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: GATA1-related cytopenia

For Diamond-Blackfan anemia (Orphanet):

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

Similar variants

GATA1 p.Ser36fs Pathogenic ★ same residue
GATA1 c.220+1G>A Pathogenic ★★ same condition
GATA1 c.220+2T>C Pathogenic/Likely pathogenic ★★ same condition
GATA1 p.Arg216Gln Pathogenic ★★ same condition
GATA1 p.Arg216Trp Likely pathogenic ★★ same condition
GATA1 p.Met1Thr Pathogenic/Likely pathogenic ★★ same condition
GATA1 p.Ser12Ter Pathogenic/Likely pathogenic ★★ same condition
GATA1 p.Ser30Ter Pathogenic ★★ 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/gata1-p-ser36phe (accessed [today's date]).

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