Is TERF2IP p.Val264Phe (c.790G>T) pathogenic?

TERF2IP p.Val264Phe (c.790G>T) is classified Uncertain significance in TERF2IP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-21). AlphaMissense: likely benign (0.1191); Very rare (popmax 0.0011%, sas).

How common is TERF2IP p.Val264Phe (c.790G>T) in the general population?

TERF2IP p.Val264Phe (c.790G>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about TERF2IP p.Val264Phe (c.790G>T)?

AlphaMissense predicts likely benign (score 0.1191) — an in-silico prediction, not a clinical call.

TERF2IP p.Val264Phe

c.790G>T · rs776321445 · VCV1761187

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1191 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1191	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -8.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.41	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7	GERP 0.51, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 8,725 bp · p 0.011 · regional, not allelic
Overall
CADD	17.67	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.0011% South Asian · 1/91,022 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,460,194 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,022
European (non-Finnish)	0.00017%	589,543

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.Val264Phe
Coding: c.790G>T
MANE Select: NM_018975
dbSNP: rs776321445
Type: single nucleotide variant
Location: chr16:75654392 (GRCh38)
Gene constraint: LOEUF 1.45 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.76 · 5 PDB
Residue 264: the 'disordered' region

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

Similar variants

TERF2IP p.Val264Ala Uncertain significance ★★ ⚠ same residue
TERF2IP p.Val264Ile 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.Ala61Thr Uncertain significance ★★ ⚠ same type
TERF2IP p.Ala65Thr Uncertain significance ★★ ⚠ same type
TERF2IP p.Arg133Gln 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-val264phe (accessed [today's date]).

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