Is TERF2IP p.Pro103Ser (c.307C>T) pathogenic?

TERF2IP p.Pro103Ser (c.307C>T) is classified Conflicting classifications of pathogenicity in TERF2IP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-05-26). AlphaMissense: likely benign (0.0706); Ultra-rare (popmax 0.0296%, amr).

How common is TERF2IP p.Pro103Ser (c.307C>T) in the general population?

TERF2IP p.Pro103Ser (c.307C>T) is ultra-rare (popmax 0.0296%, amr) (gnomAD).

What do computational predictors say about TERF2IP p.Pro103Ser (c.307C>T)?

AlphaMissense predicts likely benign (score 0.0706) — an in-silico prediction, not a clinical call.

TERF2IP p.Pro103Ser

c.307C>T · rs760421834 · VCV1727350

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0706 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0296%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0706	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -5.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.52	GERP -3.5
Regional constraint	o/e 1.11	unconstrained · MANE · 8,725 bp · p 0.011 · regional, not allelic
Overall
CADD	1.77	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 0.0296% Admixed American · 15/50,696 alleles

Filtering AF 0.0182% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00812% 126/1,551,712 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0296%	3,380
European (non-Finnish)	0.00895%	11,172
African / African-American	0.00678%	14,756
Remaining individualsnot grpmax-eligible	0.00499%	20,033

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: TERF2IP
Protein: p.Pro103Ser
Coding: c.307C>T
MANE Select: NM_018975
dbSNP: rs760421834
Type: single nucleotide variant
Location: chr16:75648189 (GRCh38)
Gene constraint: LOEUF 1.45 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.76 · 5 PDB

Full TERF2IP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TERF2IP p.Pro103Leu Uncertain significance ★★ ⚠ same residue
TERF2IP p.Pro103Thr Uncertain significance ★★ ⚠ same residue
TERF2IP p.Pro103= Likely benign ★★ same residue
TERF2IP p.Pro103Ala Uncertain significance ★ ⚠ same residue
TERF2IP p.Ala123Gly Uncertain significance ★★ ⚠ same type
TERF2IP p.Ala200Gly Uncertain significance ★★ ⚠ same type
TERF2IP p.Ala387Val Uncertain significance ★★ ⚠ same type
TERF2IP p.Ala61Thr Uncertain significance ★★ ⚠ 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/terf2ip-p-pro103ser (accessed [today's date]).

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