What condition is associated with POT1 p.Thr628= (c.1884A>C)?

POT1 p.Thr628= (c.1884A>C) is associated with pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 8, tumor predisposition syndrome 3, hereditary neoplastic syndrome (ClinVar).

POT1 p.Thr628=

Q: Is POT1 p.Thr628= (c.1884A>C) pathogenic?

POT1 p.Thr628= (c.1884A>C) is classified Benign in POT1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 11.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 8.

Q: How common is POT1 p.Thr628= (c.1884A>C) in the general population?

POT1 p.Thr628= (c.1884A>C) is common (popmax 11.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1884A>C · rs17147565 · VCV475068

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 11.2%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.039	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.94	GERP -3.3, phastCons 0.001
Overall
CADD	6.538	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.2% African / African-American · 8,348/74,256 alleles

Filtering AF 11% ClinGen BA1/BS1 input FAF95, joint · FAF99 11%

Overall 0.59% 9,370/1,588,362 alleles · common exomes 4,607/1,436,254 · genomes 4,763/152,108 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11.2%	9
Admixed American	0.725%	138
Remaining individualsnot grpmax-eligible	0.71%	141
Middle Eastern	0.35%	286
South Asian	0.0267%	3,752
European (non-Finnish)	0.00933%	10,722

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: POT1
Protein: p.Thr628=
Coding: c.1884A>C
MANE Select: NM_015450
dbSNP: rs17147565
Type: single nucleotide variant
Location: chr7:124823983 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 87.63 · 14 PDB

Full POT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: tumor predisposition syndrome 3 hereditary neoplastic syndrome cerebroretinal microangiopathy with calcifications and cysts 3

Similar variants

POT1 p.Thr628Ile Uncertain significance ★★ ⚠ same residue
POT1 p.Thr628Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
POT1 c.10-2A>C Pathogenic/Likely pathogenic ★★ same condition
POT1 c.1163+1G>A Likely pathogenic ★★ same condition
POT1 c.1164-1G>A Pathogenic/Likely pathogenic ★★ same condition
POT1 c.124+1G>C Pathogenic/Likely pathogenic ★★ same condition
POT1 c.124+2T>C Likely pathogenic ★★ same condition
POT1 c.125-2A>G Likely 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/pot1-p-thr628 (accessed [today's date]).

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