Is TEX14 p.Arg6Ser (c.16C>A) pathogenic?

TEX14 p.Arg6Ser (c.16C>A) is classified Uncertain significance in TEX14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely benign (0.1272); Rare (popmax 0.718%, afr).

How common is TEX14 p.Arg6Ser (c.16C>A) in the general population?

TEX14 p.Arg6Ser (c.16C>A) is rare (popmax 0.718%, afr) (gnomAD).

What do computational predictors say about TEX14 p.Arg6Ser (c.16C>A)?

AlphaMissense predicts likely benign (score 0.1272) — an in-silico prediction, not a clinical call.

TEX14 p.Arg6Ser

c.16C>A · VCV4183118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1272 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.718%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1272	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -5.64	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 6.9	GERP -0.99, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 50 kb · p 3.6e-05 · regional, not allelic
Overall
CADD	17.25	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 0.718% African / African-American · 532/74,088 alleles

Filtering AF 0.668% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.648%

Overall 0.0386% 614/1,592,536 alleles · rare exomes 324/1,440,318 · genomes 290/152,218 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.718%	139
Admixed American	0.0568%	1,760
Middle Eastern	0.0502%	1,991
Remaining individualsnot grpmax-eligible	0.044%	2,274
South Asian	0.00231%	43,382
European (non-Finnish)	0.00162%	61,696

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: TEX14
Protein: p.Arg6Ser
Coding: c.16C>A
MANE Select: NM_031272
Type: single nucleotide variant
Location: chr17:58651986 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.95 · 2 PDB

Full TEX14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TEX14 p.Arg6Cys Uncertain significance ★ ⚠ same residue
TEX14 p.Arg6His Likely benign ★ same residue
TEX14 p.Glu1351Gly Uncertain significance ★★ ⚠ same type
TEX14 c.2789-7T>C Benign ★★ same type
TEX14 c.3717+7A>G Likely benign ★★ same type
TEX14 p.Leu1380Phe Benign/Likely benign ★★ same type
TEX14 p.Thr979= Benign ★★ same type
TEX14 c.4267+1G>A Likely pathogenic ★ 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/tex14-p-arg6ser (accessed [today's date]).

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