Is TERF2 p.Pro322Gln (c.965C>A) pathogenic?

TERF2 p.Pro322Gln (c.965C>A) is classified Benign/Likely benign in TERF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-14). AlphaMissense: likely benign (0.1166); Low-frequency (popmax 1.96%, afr).

How common is TERF2 p.Pro322Gln (c.965C>A) in the general population?

TERF2 p.Pro322Gln (c.965C>A) is low-frequency (popmax 1.96%, afr) (gnomAD).

What do computational predictors say about TERF2 p.Pro322Gln (c.965C>A)?

AlphaMissense predicts likely benign (score 0.1166) — an in-silico prediction, not a clinical call.

TERF2 p.Pro322Gln

c.965C>A · rs34014829 · VCV714711

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1166 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.96%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1166	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -7.23	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 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 11 kb · p 0.093 · regional, not allelic
Overall
CADD	25.5	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 1.96% African / African-American · 1,470/74,848 alleles

Filtering AF 1.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.85%

Overall 0.102% 1,647/1,609,094 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.96%	51
Middle Eastern	0.182%	550
Remaining individualsnot grpmax-eligible	0.124%	809
Admixed American	0.082%	1,220
South Asian	0.0044%	22,742
European (non-Finnish)	0.00306%	32,669

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: TERF2
Protein: p.Pro322Gln
Coding: c.965C>A
MANE Select: NM_005652
dbSNP: rs34014829
Type: single nucleotide variant
Location: chr16:69367182 (GRCh38)
Gene constraint: LOEUF 0.444 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.36 · 18 PDB
Residue 322: the 'disordered' region

Full TERF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TERF2 c.1341-42T>C Benign ★★ same type
TERF2 c.1426+95C>T Benign ★★ same type
TERF2 c.380-5C>T Benign ★★ same type
TERF2 c.840+145C>T Benign ★★ same type
TERF2 c.947+27G>A Benign ★★ same type
TERF2 c.*142G>A Benign ★★ same type
TERF2 c.*159C>T Benign ★★ same type
TERF2 c.*220A>G Benign ★★ 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/terf2-p-pro322gln (accessed [today's date]).

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