Is BLM p.Thr738Pro (c.2212A>C) pathogenic?

BLM p.Thr738Pro (c.2212A>C) is classified Uncertain significance in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-27). AlphaMissense: likely pathogenic (0.8932); Absent from gnomAD v4.1.

How common is BLM p.Thr738Pro (c.2212A>C) in the general population?

BLM p.Thr738Pro (c.2212A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BLM p.Thr738Pro (c.2212A>C)?

AlphaMissense predicts likely pathogenic (score 0.8932) — an in-silico prediction, not a clinical call.

BLM p.Thr738Pro

c.2212A>C · VCV4687756

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8932 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8932	likely pathogenic
REVEL	0.333	indeterminate
SaProt	LLR -12.85	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BLM
Protein: p.Thr738Pro
Coding: c.2212A>C
MANE Select: NM_000057
Type: single nucleotide variant
Location: chr15:90766928 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 61.10 · 16 PDB
Residue 738: the helicase atp-binding domain

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

Similar variants

BLM p.Thr738Ala Uncertain significance ★★ ⚠ same residue
BLM p.Thr738Arg Uncertain significance ★★ ⚠ same residue
BLM p.Thr738Ile Uncertain significance ★★ ⚠ same residue
BLM p.Thr738= Likely benign ★★ same residue
BLM p.Thr738Ser Uncertain significance ★ ⚠ same residue
BLM p.Thr738delinsIlePro Likely benign ★ same residue
BLM p.Thr738fs Likely benign ★ same residue
BLM c.1087+1G>A Likely pathogenic ★★ 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/blm-p-thr738pro (accessed [today's date]).

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