Is POT1 p.Asp313= (c.939C>T) pathogenic?

POT1 p.Asp313= (c.939C>T) is classified Benign/Likely benign in POT1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-20). Ultra-rare (popmax 0.0517%, sas); Associated with pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 8.

What condition is associated with POT1 p.Asp313= (c.939C>T)?

POT1 p.Asp313= (c.939C>T) is associated with pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 8, tumor predisposition syndrome 3, hereditary neoplastic syndrome (ClinVar).

How common is POT1 p.Asp313= (c.939C>T) in the general population?

POT1 p.Asp313= (c.939C>T) is ultra-rare (popmax 0.0517%, sas) (gnomAD).

POT1 p.Asp313=

c.939C>T · rs746756338 · VCV823207

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0517%, sas)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 1.8, phastCons 1
Overall
CADD	5.755	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0517% South Asian · 47/90,864 alleles

Filtering AF 0.0399% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0358%

Overall 0.00305% 49/1,606,678 alleles · ultra-rare exomes 46/1,454,370 · genomes 3/152,308 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0517%	1,933
Remaining individualsnot grpmax-eligible	0.00321%	31,124

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.Asp313=
Coding: c.939C>T
MANE Select: NM_015450
dbSNP: rs746756338
Type: single nucleotide variant
Location: chr7:124851882 (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.Asp313Tyr Uncertain significance ★★ ⚠ same residue
POT1 p.Asp313Val Uncertain significance ★★ ⚠ same residue
POT1 p.Asp313Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
POT1 p.Asp313Gly Uncertain significance ★ ⚠ same residue
POT1 p.Asp313His Uncertain significance ★ ⚠ 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

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-asp313 (accessed [today's date]).

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