Is TERF2IP p.Ala61Val (c.182C>T) pathogenic?

TERF2IP p.Ala61Val (c.182C>T) is classified Uncertain significance in TERF2IP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). AlphaMissense: likely pathogenic (0.7994); Very rare (popmax 0.000257%, nfe).

How common is TERF2IP p.Ala61Val (c.182C>T) in the general population?

TERF2IP p.Ala61Val (c.182C>T) is very rare (popmax 0.000257%, nfe) (gnomAD).

What do computational predictors say about TERF2IP p.Ala61Val (c.182C>T)?

AlphaMissense predicts likely pathogenic (score 0.7994) — an in-silico prediction, not a clinical call.

TERF2IP p.Ala61Val

c.182C>T · VCV4722360

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7994 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000257%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7994	likely pathogenic
REVEL	0.126	moderately benign-leaning
SaProt	LLR -10.74	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 8,725 bp · p 0.011 · regional, not allelic
Overall
CADD	28.8	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 0.000257% European (non-Finnish) · 3/1,168,424 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000209% 3/1,437,868 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: TERF2IP
Protein: p.Ala61Val
Coding: c.182C>T
MANE Select: NM_018975
Type: single nucleotide variant
Location: chr16:75648064 (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.Ala61Thr Uncertain significance ★★ ⚠ same residue
TERF2IP p.Ala61= Likely benign ★ 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.Ala65Thr Uncertain significance ★★ ⚠ same type
TERF2IP p.Arg133Gln Uncertain significance ★★ ⚠ same type
TERF2IP p.Arg378Ser 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-ala61val (accessed [today's date]).

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