Is TERF2IP p.Arg211Trp (c.631C>T) pathogenic?

TERF2IP p.Arg211Trp (c.631C>T) is classified Uncertain significance in TERF2IP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-08). AlphaMissense: ambiguous (0.4175); Absent from gnomAD v4.1.

How common is TERF2IP p.Arg211Trp (c.631C>T) in the general population?

TERF2IP p.Arg211Trp (c.631C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TERF2IP p.Arg211Trp (c.631C>T)?

AlphaMissense predicts ambiguous (score 0.4175) — an in-silico prediction, not a clinical call.

TERF2IP p.Arg211Trp

c.631C>T · rs2507075274 · VCV1752830

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4175 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,579,332)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4175	ambiguous
REVEL	0.24	benign-leaning
SaProt	LLR -13.14	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.5	GERP 0.8, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 8,725 bp · p 0.011 · regional, not allelic
Overall
CADD	28.1	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

No allele count reported in gnomAD v4.1 (AN 1,579,332). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TERF2IP
Protein: p.Arg211Trp
Coding: c.631C>T
MANE Select: NM_018975
dbSNP: rs2507075274
Type: single nucleotide variant
Location: chr16:75648513 (GRCh38)
Gene constraint: LOEUF 1.45 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.76 · 5 PDB
Residue 211: the 'disordered' region

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

Similar variants

TERF2IP p.Arg211Gln 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
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-arg211trp (accessed [today's date]).

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